Comparative structural analysis of desmoplakin, bullous pemphigoid antigen and plectin: members of a new gene family involved in organization of intermediate filaments Kathleen J. Green* and Maria Luisa A. Virata Northwestern University Medical School, Department o f Pathology and the Cancer Center, 303 E. Chicago Ave., Chicago, IL 60611, USA

George W. Elgart and John R. Stanley Dermatology Branch, National Cancer Institute, NIH, Bethesda, M D 20892, USA

and David A. D. Parry Department o f Physics and Biophysics, Massey University, Palmerston North, New Zealand

(Received 16 December 1991) Desmoplakins ( DP ) and bullous pemphiooM antigen ( BPA ) are major plaque components o f the desmosome and hemidesmosome, respectively. These cell adhesion structures are both associated intimately with the intermediate filament (IF) network. Structural analyses of DP and BPA sequences have indicated that these molecules are likely to form extended dumbbell-shaped dimers with a central rod and globular end domains. Recent sequence data have indicated that the N-terminal domains o f both DP and BPA (like their C-terminal domains) are highly related." the former contain regions o f heptad repeats that ate predicted to form several a-helical bundles. Comparisons o f DP and BPA protein sequences with that o f plectin (PL), a 466 kDa IF-associated protein, have also revealed large scale homology. Identities between their N-terminal domains are: DP: BPA = 35%, DP: P L = 32%, BPA: PL = 40%, suggesting that BPA is more closely related to PL than DP in this region. In the C-terminal domains, which contain a 38-residue repeating motif, however, DP and PL are closer relatives (identities: DP: BPA = 38%, BPA: PL = 40%, DP: PL = 49%). The central domains o f all three proteins have extensive heptad repeat substructure, express the same periodic distribution o f charged residues, and are predicted to form two-stranded a-helical coiled-coil ropes. These observations suggest that DP, BPA and PL belong to a new gene family encoding proteins involved in IF organization. Keywords: Intermediatefilaments;desmosomes;hemidesmosomes

Introduction Intermediate filaments (IF) are major components of the eukaryotic cytoskeleton and nuclear envelope1-3. Unlike the other two major cytoskeletal systems, microfilaments and microtubules, IF are an extremely diverse family of proteins, comprising six major classes of polypeptides that display distinct, developmental and tissue-specific patterns of expression. Cytoplasmic IF are organized into extensive networks that are crosslinked to varying degrees depending on the tissue and cell type 2'4. Furthermore, a number of intermediate filamentassociated proteins have been described as possible mediators of I F - I F interactions in the cytoplasm 1'5'6 . Cytoplasmic IF networks also associate with organelles, the nuclear surface and the cell s u r f a c e 4 ' 7 ' 8 . In epithelia and certain other specialized tissues, desmosomes act as the cell surface attachment sites at points of cell-cell *To whomcorrespondenceshould be addressed. 0141-8130/92/030145-09 © 1992Butterworth-HeinemannLimited

contact. Hemidesmosomes perform this function at sites of cell-substrate contact 8'9. In spite of the similar role played by these adhering-type junctions, recent evidence indicates that the hemidesmosome is not strictly speaking a half desmosome9'1°. In fact, these junctions are composed of immunologically distinct molecules that now appear to be related in some cases as determined by characterization of cloned cDNAs. The major components in the cytoplasmic plaque of hemidesmosomes and desmosomes are high molecular weight polypeptides known as bullous pemphigoid antigen (BPA) and desmoplakins (DP), respectively 8'9'1 ~. Immunolocalization analysis at the electron microscope level indicates that these proteins are found in the region of IF attachment. Intriguingly, an initial comparison of the predicted amino acid sequence of these molecules indicated a striking similarity in their C-terminal domains 12"a3, and in fact it was suggested that these molecules may define a new family of cell adhesion junction plaque proteins 14.

Int. J. Biol. Macromol., 1992, Vol. 14, June

145

Desmoplakin, BP antigen and plectin: K. J. Green et al. This observation became even more interesting in light of a recent report that a known intermediate filamentassociated protein (IFAP) called plectin (PL) also displays a striking homology to both DP and BPA in its C-terminal domain 15. This protein of molecular weight 466kDa is present in minor amounts in desmosomes. However, it is not restricted to adhesive junctions but is also widely distributed within the cytoplasm of most tissues and cell types 16. Interestingly, it is most highly abundant in skeletal muscle which does not contain desmosomes. In vitro binding studies have suggested that PL, unlike BPA and DP, can bind to vimentin, lamins, microtubules and many other cytoskeletal-related proteins, and thus it is thought to act as a universal linking protein t6. In the present work we have examined the relationship between these three proteins in more detail, including in our analysis an investigation of the amino terminal domains for which sequence data have only recently become available. Our results confirm and extend observations by Green et al. Iz, Tanaka et al. 14, Sawamura et al. 17, and Wiche et al. 15, suggesting that each of these protein molecules is built along the same basic structural plan, with a central e-helical coiled-coil rod domain, flanked by a pair of globular N-terminal domains and a pair of globular C-terminal domains. Although the sequences of the central domain have apparently diverged significantly, the heptad repeat and periodicity of acidic and basic residues have been maintained. Comparison of the N-terminal domains has revealed extensive regions of striking homology and these are outlined here for the first time. In addition, this three-way comparison has allowed us to make modifications in the previously reported boundaries of the rod domains for each molecule. Together, these data indicate that DP, BPA and PL establish a new gene family that encodes proteins related to the organization of IF networks.

Experimental Computer analysis Initial sequence input, comparisons, translations, searches for consensus sequences, and secondary structural predictions were performed using the AASAP (Amino Acid Sequence Analysis Program) and PC Gene software package (Intelligeneties, Mountain View, CA). In the comparison of sequences the following groupings were considered homologous: D/E, K/R, S/T and L/I/V/M/F/Y/A. Dot matrix comparisons were performed using the COMPARE and DOTPLOT programs on UWGCG (University of Wisconsin Genetic Computer Group) 18 running on the Northwestern University Biochemistry (BMBCB) VAX. Fast Fourier transform (FFT) analyses to determine the periodic distribution of residues (charged or apolar) were carried out as previously described by McLachlan and Stewart 19. Interchain ionic interactions were calculated between heptad-containing e-helical segments as a function of their relative axial stagger 2°'21 and although previous work by Conway and Parry 22 has shown that the chains in all two-stranded coiled-coils are parallel and in axial register (stabilized by 0.23-0.77 ionic interactions per heptad pair) this was not assumed here and a full range of alternatives was investigated. Lengths of coiled-coil segments were calculated as the product of the number

146 Int. J. Biol. Macromol., 1992, Vol. 14, June

of residues in the segment having a heptad substructure and the axial rise per residue (0.1485 nm) established by X-ray diffraction for this conformation. The ratio of charged (D, E, K, R) to apolar (L, I, V, M, F, Y, A) residues was also calculated for various segments. This is a simple and useful parameter 23 that can be related to the overall shape of a protein segment. Typically, elongate domains (such as a two-strand coiled-coil rope) have ratios > 1, and more globular domains (such as a bundle of e-helices) have ratios ~ 0.8 or less.

Results and discussion Comparative analysis of the DP, BPA and PL rod domains As described previously, the central domain of each molecule contains a repeating heptad pattern of the type (a, b, e, d, e, f, 9),, where a and d are predominantly apolar 12'14'15. This pattern indicates that each molecule will form an e-helical coiled-coil. The conservation of the repeating heptad motif is reflected by numerous points off the diagonal in this region of each DOTPLOT (Fioure 1). Similar DOTPLOT patterns are seen when the rod domains of these molecules are compared with other, unrelated molecules containing e-helical coiledcoils. In contrast, in regions of high homology, such as that seen in the N- and C-terminal domains of DP, BPA and PL, the majority of dots are found in a continuous line along the diagonal (Figure 1). In addition to the short range heptad repeat, FFT has revealed significant periodicities of acidic and basic residues along the length of each rod domain ( Table 1). As reported previously by Green et al. 12, the entire rod of DP is characterized by a periodicity of 10.4 residues in the linear disposition of the acidic and basic residues (Table 1). The patterns of periodicities in BPA and PL are more complicated in that they display region-specific differences. In these molecules the rod domains are interrupted by sequences that lack a regular heptad substructure and which are predicted to be non-helical (Figure 2). In BPA one of these interruptions extends from residue 1327 to 1354. (It should be noted that the numbering used here corresponds to that recently published by Sawamura et al. 17, with 1 beginning at the first methionine. This corresponds to 773-800 in Tanaka et al. 14. For a discussion of the extent of each rod domain, see below.) A period of ~ 10.5 in the acidic and basic residues is present in the N-terminal region of the rod (length 27.0 nm), whereas a period of ,-~10.2 residues is present on the C-terminal side of the interruption (length 76.5 nm) (Table 1). Wiche et al. 15 reported a period of 10.4 residues along the PL rod. However, when the PL rod is divided into three predicted e-helical regions based on the maintenance of heptad substructure as shown in Figure2, it becomes apparent that each displays a somewhat different periodicity. Residues 947 1563 (length 91.6 nm) display a periodicity of ~ 10.5 residues; residues 1666-1710 (length 6.7 nm), which are very rich in the e-helix-favouring residues alanine and glutamic acid, display a periodicity of ~ 10.1 residues; residues 1746-2070 (length 48.3 nm) display a periodicity of 10.2 residues (Table 1). In each case, the periodicities in acidic and basic residues are out of phase by ~ 180°, suggesting a potential mechanism of self-aggregation mediated by ionic interactions in the rod domains. The first non-e-helical region between sections of coiled-coil

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(residues 1564-1665) is extremely basic, as noted previously by Wiche et al) 5, and is predicted to contain turn, coil and # structure. Surprisingly, this region maintains a 10.4 residue period, but only in the distribution of basic residues. The second non-helical region (residues 1711-1745) is very rich in glycine

residues (46%), comprising a near 2-residue repeat of G-X, and contains four prolines. It is predicted to be highly flexible with elements offl, turn and coil structure. A three-way comparison of DP, BPA and PL indicates that some revision of the previously reported extent of the rod boundaries is warranted. Using D O T P L O T , the heptad-containing regions of the rod domains become highly accentuated as a rectangular array of dots off the diagonal, as do the regions of more extensive homology in the N-terminal domain (Figure 1). The original designation for the rod boundaries for each molecule was obscured by the fact that the substructure of the amino-terminal domain of each molecule is also based on a heptad repeat (see below). These regions can be distinguished from each other, however, because in the N-terminus there is a lack of long-range periodicity in the acidic and basic residues, there are more extensive and exact regions of homology among the molecules, and there is a much lower ratio of charged to apolar residues that favours a compact rather than a rope-like structure (Tables 1 and 2). Based on these criteria the boundaries of the D P rod are likely to be 863-1751 as recently reported 25 (Figure 2). The boundaries for the rod of BPA have been reported variously as 154-131514, which is equivalent to 708-1869 with the addition of the recently determined N-terminal sequence, and as 875-181317 . Based on the criteria described above, however, the actual boundaries are likely to be 1145-1869. This new rod for BPA finishes at precisely the same place reported by Tanaka et al. 14 with regards to its C-terminus, but the amino terminal end of the original rod is now considered to be part of the amino terminal domain, and contains regions of high homology with both D P and PL (Fiyures 3 and 4). As described in more detail below, the low charged/apolar ratio and low ionic interactions in D P favour a compact arrangement of e-helices in this homologous region (Table 2). It should be noted, however, that the higher number of possible interchain ionic interactions in this region of BPA (Table 2) leaves open the possibility of a section of coiled-coil rod within the amino terminal domain. The minimum length of the new rod in BPA would be ~ 1 0 4 n m . The length of the non-helical segment between segments of the BPA coiled-coil is unknown but is unlikely to be more than ~ 6 nm, thus generating a total rod domain of ~ 104-110 nm. Wiche et al. 15 proposed that the PL rod begins at residue 700 and extends to 2100, although the authors stated as a caveat that the heptad substructure is much more pronounced beginning at residue 930. The less regular region from 700 to 930 was thus divided in their model into a separate R1 domain and the remainder of the rod into R2 which contains five homologous regions. In light of our current three-way comparisons, it is clear that the R1 region is likely to be part of the N-terminal domain, as it contains regions of very high homology with the BPA and D P N-terminal domains. In addition, this region has zero net ionic interactions to stabilize a two chain coiled-coil, and has a low charged/apolar ratio (Table2). We suggest that the boundaries should be revised to 947-2070 making the plectin rod 1124 residues in extent as compared with 889 residues for D P and 725 residues for BPA. The predicted length of the PL rod domain would be about 147 nm plus an allowance for the two non-heptad-containing segments. The observed length of 190 nm is thus consistent with our model 24.

Int. J. Biol. Macromol., 1992, Vol. 14, June

147

Desmoplakin, BP antigen and plectin." K. J. Green et al. Table 1

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148

Int. J. Biol. Macromol., 1992, Vol. 14, June

Desmoplakin, BP antigen and plectin: K. J. Green et al. Table 2 Structural features of desmoplakin I, bullous pemphigoid antigen and plectin DPI

N-terminal domain Extent (residues) Charged/apolar ratio Whole domain Heptad regions only No. of interchain ionic interactions per heptad pair Rod domain Extent (residues) Charged/apolar ratio Whole domain Heptad regions only No. of interchain ionic interactions per heptad pair Predicted length (nm) C-terminal domain Extent (residues) Charged/apolar ratio Whole domain

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Comparative analysis of DP, BPA and PL N-terminal domains A three-way comparison of the amino terminal sequences of each molecule revealed significant homology in primary sequence (Figure4) as well as predicted secondary structure. Based on the new rod boundaries,

this domain runs from ! - 8 6 2 in DP, 1-1144 in BPA, and 1-946 in PL. A comparison of D P and BPA reveals four major homologous regions in which the overall identity is 35%, whereas a comparison between D P and PL reveals six regions with an identity of 32% (Figures 2 and 3). The identity between BPA and P L is greatest with 40% of the residues being identical throughout four major regions of homology (Fioures 2 and 3). On the basis of homology these percentages are 54, 52 and 59%, respectively. Each molecule can also be divided into different regions based on the predicted secondary structure, as proposed for D P 25. Based on Garnier 26 and C h o u / F a s m a n 27 analysis the amino terminal domain of each molecule has significant regions of a-helical content, consistent with the observation that there is a discontinuous heptad repeat substructure throughout much of this domain. Unlike the rod, however, the charged/apolar ratio for these regions is low, 0.72 for DP, 0.83 for PL and 0.80 for BPA, indicating a propensity for bundles of antiparallel a-helices, rather than a two-chain coiled-coil (Table 2). In addition, the number of ionic interactions that could stabilize a parallel two-chain coiled-coil decreases significantly in this region. For D P it has been proposed that there are two major heptad-containing regions V and Y, each with five a-helical antiparallel strands 19, and three minor ones designated W (with three strands) and X and Z (each with two strands). Both BPA and PL can also be divided into similar regions, as demonstrated in Figure 4. In BPA and PL, there is also an additional region designated in Figure 4 as NN, predicted to comprise several short stretches of a-helix. The resulting prediction is thus that the overall structure of the N-terminal domains will be an elongated globule containing several bundles of antiparallel a-helices. This is consistent with published rotary shadowed images of D P 28 and PL z4.

Comparative analysis of DP, BPA and PL C-terminal domains The C-terminal domains of DP, BPA and PL each comprise a series of repeats in the primary sequence,

Int. J. Biol. Macromol., 1992, Vol. 14, June

149

Desmoplakin, BP antigen and plectin." K. J. Green et al. lip

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S E L E

Figure 4 Three-way sequence alignment of the N-terminal domains of BPA, PL and DP. Identical residues are shaded. Boundaries of the conserved heptad-rich predicted ~-helical bundles designated Z, Y, X, W and V are indicated between the arrows. An additional region of homology (NN) shared by BPA and PL, predicted to contain short ~t-helices, is likewise indicated. Our BPA sequence differs from that reported by Sawamura et al. ~7 at residues 851 (V vs. G) and 1644 (R vs. T)

150

Int. J. Biol. Macromol., 1992, Vol. 14, June

Desmoplakin, B P antigen and plectin: K. J. Green et al.

organized into discrete subdomains that were first described in D P ~2. Within the boundaries of the D P C-terminal domain three subdomains called A (residues 1832-2007), B (residues 2075-2250) and C (residues 2434-2609) were described. As a result of refining the rod boundaries, this entire domain is now predicted to consist of 926 residues running from 1752-26772~. BPA has only two of these subdomains (residues 2•48 2321 and 2457-2632) within its 780 residue C-terminal domain which runs from 1870-2649. PL has six subdomains (residues 2299-2474; 2627-2803; 29593134; 3294-3468; 3537-3712; 3882-4057) extending within a C-terminal domain of 2070 residues running from 2071-4140. When three-way comparisons are performed it is evident that the highest degree of homology is in the last two domains of each molecule (Figure 5). The subdomain designation can be stated as A-B-C for DP, B-C for BPA and B-B-B-B-B-C for PL. Interestingly, the closest relatives on the basis of sequence identity are PL and D P (DP:BPA = 38%, BPA:PL = 4 0 % and D P : P L -- 49%); on the basis of homologies these figures rise to 59, 60 and 64%, respectively. There has been some disagreement as to the underlying oe

BP

OP

2oo7

repeating unit within the 176 residue subdomains. Green et al. az and T a n a k a et al. 1~ described a 38-residue repeat in D P and BPA, whereas Wiche et al. ~ reported a 19residue repeating unit in PL. Both F F T analysis and comparisons a m o n g possible repeat units indicate that the underlying structural repeat is indeed 38 residues (or a multiple) whereas the best chemical repeat is 76 residues. For instance, F F T of the five B repeats and one C repeat in PL indicates a strong periodicity of 9.53 residues (acidic) and 9.54 residues (basic) in addition to a period of 5.39 residues (acidic) and 5.43 residues (basic). The latter period indexes easily as the seventh order of 38 residues, i.e. 5.43. It cannot be accounted for by a 19-residue period. However, the true period could still be a multiple of 38 residues. The calculated number of identities for 19-, 38- and 76- residue repeats in the C-terminal subdomain structure of PL suggest that the best chemical repeat is 76 residues. The secondary structure predicted for these 176-residue repeats consists of five antiparallel :(-helices linked by/%turns ~~. It differs significantly from that proposed by Wiche et al. ~ . It is worth noting that these larger repeating domains are followed by a smaller repeating motif G-S-R-X in both

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Int. J. Biol. Macromol., 1992, Vol. 14, June

151

Desmoplakin, BP antigen and plectin: K. J. Green et al. region encompassing the last two subdomains of the repeat structure) (Figure 6). Recently, Sawamura et al. 17 suggested that BPA is a transmembrane molecule with a 17 amino acid membrane-spanning domain running from residue 2165 to 2181 within the first subdomain (B domain) of the C-terminal domain. They suggested, furthermore, that the first 43 residues of their sequence represent a possible signal peptide. Based on several criteria, this proposal seems unlikely. First, the prediction for both the transmembrane and signal sequences are very weak. The program HELIXMEM in PC Gene does not predict a transmembrane sequence in BPA, and the predictions by SOAP and RAOARGOS are borderline. Perhaps most importantly, it follows from the location of the putative transmembrane spanning domain and signal sequences that about 80% of BPA would lie outside the cell, including a small portion of the C-terminus. This seems highly unlikely since by homology with DP, a cytoplasmic protein, and by immunogold localization of C-terminal epitopes, the C-terminal domain of BPA would seem to be completely restricted to the cytoplasmic face of the hemidesmosome ~1 Although it is clear that these molecules display extensive similarities as outlined above, it is the regions of divergence that may reflect the functional differences. From biochemical and morphological studies it is clear that these proteins must have distinct sequences or subdomains that provide different functional characteristics. For instance, the distribution and binding partners of PL are much more wide ranging than for either BPA

PL and DP, but not in BPA. The last of three repeats is modified to a consensus target sequence for protein kinase A, G-S-R-R-G-S. The G-S-R-X- motif is followed by four copies of yet another repeat, Y/F-S in DP and PL. Again this sequence is absent from BPA. The results presented here confirm and extend the observations that DP, BPA and PL are not only highly related in their primary sequences, but are also likely to take on similar higher order structural conformations lz'14,ls (Figure 6). That is, each is likely to form a dumbbell-shaped dimer, with a long central coiled-coil rod domain flanked by globular end domains. In all cases, the continuity of the heptad substructure of the rod domains is broken at a number of points along their length, sometimes by quite substantial stretches of non-e-helical structure. These points probably represent regions of enhanced flexibility or perhaps kinks in the structure. The previously reported similarity in the C-terminal domains can now be extended to their N-terminal domains as well. Furthermore, the predicted secondary structure of the N-terminal domains indicates that each will take on an elongated globular conformation, containing a number of e-helical bundles. Because of the high regions of homology in the N- and C-terminal domains, it is logical to consider that their function as well as their structure may be similar. In this regard, it is important to note that, of the proteins considered here, BPA and PL show the greatest similarities in their N-terminal domains and in the organization of their rod domains, whereas PL and DP show more similarities in their C-terminal domains (particularly with regard to the

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152 Int. J. Biol. Macromol., 1992, Vol. 14, June

Desmoplakin, BP antigen and plectin: K. J. Green et al. or DP. Furthermore, BPA is restricted to the hemidesmosome and DP is restricted to the desmosome, indicating special 'localization' signals. The extended rod length of PL may carry unique functional motifs that may account for the number and diversity of binding sites and partners (Figure 6). These partners include vimentin and lamin B whose interaction with plectin is thought to occur close to the centre of the rod domain ~5. Examples of structural motifs that could be involved in protein-protein interactions would be the extremely basic region in the non-a-helical portion of the rod from 1564 to 1665, and the G-X rich region from 1711 to 1745. As described above, another glycine-rich region in the form G-S-R-X is found at the very end of the PL C-terminal domain and displays a high degree of homology with the previously reported G-S-R-S motif at the end of DP. Interestingly, such a region is absent in the tail domain of BPA (Figure6). Glycine-rich peptide sequences have also been noted in nuclear lamins, keratins, loricrin, filaggrin and desmoglein 129'3°. It has been proposed that these glycine-rich sequences form loops capable of mediating weak reversible hydrophobic as well as H-bonding interactions with adjacent loops in the same molecule or with loops in neighbouring related or unrelated molecules. For example, these sequences may mediate interactions between keratin filaments, and between keratin filaments and cell envelope proteins such as loricrin z9. Finally, it is interesting to note that the human genes encoding DP and BPA have both recently been localized to chromosome 6, suggesting a gene duplication event that gave rise to these two genes 31'3z. This observation, along with the extensive sequence homologies and the similar structural predictions for all three proteins, suggests the existence of a new gene family involved in IF organization. Using a combined biochemical and molecular genetic approach, it should now be possible to define regions that play similar functions as well as regions that account for the unique functional features of these three related proteins.

Acknowledgements This work was supported by grants to KJ.G. from the National Institutes of Health (HD24430) and an American Cancer

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Society Junior Faculty Research Award.

1

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32

Jones, J. C. R., Yokoo, K. M. and Goldman, R. D. Cell Motil~ Cytoskel. 1986, 6, 560 Tanaka, T., Korman, N. J., Shimizu, H., Eady, R. A. J., Klaus-Kovtun, V., Cehrs, K. and Stanley, J. R. J. Invest. Dermatol. 1990, 94, 617 Green, K. J., Parry, D. A. D., Steinert, P. M., Virata, M. L. A., Wagner, R. M., Angst, B. D. and Nilles, L. A. J. Biol. Chem. 1990, 265, 2603 Stanley, J. R., Tanaka, T., Mueller, S., Klaus-Kovtun, V. and Roop, D. J. Clin. Invest. 1988, 82, 1864 Tanaka, T., Parry, D. A. D., Klaus-Kovtun, V., Steinert, P. M. and Stanley, J. R. J. Biol. Chem. 1991, 266, 12555 Wiche, G., Becker, B., Luber, K., Weitzer, G., Castafion, M. J., Hauptmann, R. et al. J. Cell. Biol. 19991, 114, 83 Wiche, G. Crit. Rev. Biochem. Mol. Biol. 1989, 24, 41 Sawamura, D., Li, K., Chu, M.-L. and Uitto, J. J. Biol. Chem. 1991, 266, 17784 Devereux, J., Haeberli, P. and Smithes, O. NucL Acids Res. 1984, 12, 387 McLachlan, A. D. and Stewart, M. J. Mol. Biol. 1976,103, 271 McLachlan, A. D. and Stewart, M. J. Mol. Biol. 1975, 98, 293 Parry, D. A. D., Crewther, W. G., Fraser, R. D. B. and MacRae, T. P. J. Mol. Biol. 1977, 113, 449 Conway, J. and Parry, D. A. D. Int. J. Biol. Macromol. 1991, 12, 328 Cohen, C. and Parry, D. A. D. Trends BioL Sci. 1986, 11, 245 Foisner, R. and Wiche, G. J. Mol. Biol. 1987, 198, 51519 Virata, M. L. A., Wagner, R. M., Parry, D. A. D. and Green, K. J. Proc. Natl Acad. Sci. USA 1992, 89, 544 Garnier, J., Osguthorpe, D. J. and Robson, B. J. Mol. Biol. 1978 120, 97 Chou, P. Y. and Fasman, G. D. Adv. Enzymol. 1987, 47, 45 O'Keefe, E. J., Erickson, H. P. and Bennett, V. J. Biol. Chem. 1989, 264, 8310 Steinert, P. M., Mack, J. W., Korge, B. P., Gan, S.-Q., Haynes, S. R. and Steven, A. C. Int. J. Biol. Macromol. 1991, 13, 130 Nilles, L. A., Parry, D. A. D., Powers, E. E., Angst, B. D., Wagner, R. M. and Green, K. J. J. Cell Sck 1991, 99, 809 Sawamura, D., Nomura, K., Sugita, Y., Mattei, M.-G., Chu, M.-L., Knowlton, R. and Uitto, J. Genomics 1990, g, 722 Arnemann, J., Spurr, N. K., Wheeler, G. N., Parker, A. E. and Buxton, R. S. Genomics 1991, 10, 640

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Comparative structural analysis of desmoplakin, bullous pemphigoid antigen and plectin: members of a new gene family involved in organization of intermediate filaments.

Desmoplakins (DP) and bullous pemphigoid antigen (BPA) are major plaque components of the desmosome and hemidesmosome, respectively. These cell adhesi...
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