Tarba Vol. Xl. F¶imdiaomtsdilL

No. 3. pi. 223-225. 1992.

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LETTER TO THE EDITOR CLOSTRIDIAL NEUROTOXINS-PROPOSAL NOMENCLATURE

(Receiwd

and accepted for publication

24 October

OF A COMMON

1991)

RATIONALE

toxin and the seven serologically different botulinal neurotoxins, types A through G, are synthesized in Cfostridiwn tetani and various Clostridium botulinum strains as single polypeptide chains (M, = 150,000). Upon release from the bacteria, the polypeptides are processed by endogenous or host proteases to yield highly potent neurotoxins in which the N-terminally located chain (M, = 50,000) remains disulfide-linked to a larger carboxy-terminal chain (M, = 100,000). Cloning and sequencing of the individual toxin genes revealed the close structural and functional relatedness of individual domains. Therefore, a common nomenclature should be applied for tetanus and botulinal neurotoxins. The new nomenclature should be simple and unambiguous. It should be based on structural features of the molecules, since the molecular principles underlying their mode of action remain largely obscure. TFTMNUS

PROPOSAL The terms tetanus toxin (TeTx) or botulinum toxin type A (BoNT/A) should be used for the proteolytically activated isoforms in which the individual L-chains “L” are covalently linked via a disulfide bond to the corresponding H-chains “H”. Non-cleaved, i.e. singlechain neurotoxins, as present for instance in the intact bacteria, should be specified accordingly as single-chain derivatives (e.g. sc-TeTx or sc-BoNT/E).

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224

Letter to the Editor

Previous nomenclature BoNT/A

Proposed nomenclature

TeTx

L H HN Hc

L, LC, A, a H, HC, BC, 0 0-2, H,, B ß-l, B-IIb, FC, IIc H2, C, S, B-II a-ß-2, Ibe, AB, B A-I, B-1

L-HN

L, LC, A H, HC, BC H2, B H C L-H 2

Fragments of the H-chains, as generated by additional proteolysis, should be termed Hr, (for the amino-terminal portion) and H, (for the carboxy-terminal portion), as indicated in Fig. 1 . Wherever possible, such fragments should be further characterized by the first and the last amino acid residue. Numbering should follow the codon numbers, starting at the codon number 1 which is used for initiation of translation . Thus, in the proteolytically processed TeTx, Pr02 forms the N-terminus of the L-chain, and Ser"' that of the H-chain. A fragment containing the entire L-chain of a given neurotoxin disulfide-linked to the N-terminal portion of the homologous H-chain should be termed L-HN. The corresponding fragment of tetanus toxin obtained by treatment with papain could then be further specified as L - HN(as"sa), provided that the terminae of HN have been determined . Chimeric derivatives consisting, for instance, of the L-chain of TeTx and the HN subfragment of BoNT/A should be termed L(TeTx)-HN(BoNT/A) . Of course, such specifications may be omitted if the objective is evident from the context. HEINER NmmANN Department of Microbiology, BFAV Tübingen, W-7400 Tübingen, F.R.G. The proposal has been worked out during the Fifth European Workshop on Bacterial Protein Toxins, Veldhoven, 30 June-5 July 1991 . It has been endorsed by the following groups : AGuILERA, J. Department de Bioquímica i B.M . Universitat Autdnoma de Barcelona, Spain. AHNERT-HILGER, G. Institute for Neuropsychopharmacology, Ulmenallee 30, W-1000 Berlin 19, F.R .G . BIGALKE, H. Institute of Toxicology, Medical School of Hannover, W-3000 Hannover 61, F.R .G. DAsGuPTA, B. R. Food Research Institute-UWMadison, 1925 Willow Drive, Madison, WI 53706, U.S .A . DOLLY, O. Imperial College of Science, Technology and Medicine, London SW7 2AZ, U.K. HABERMANN, E. Rudolf-Buchheim-Institute for Pharmacology, Frankfurter Str . 107, W-6300 Giessen, F.R .G . HALPERN, J. Laboratory of Bacterial Toxins, Bld. 29, 8800 Rockville Pike, Bethesda, MD 20892, U.S .A .

Letter to the Editor HEYNINGEN, VAN S . MIDDLEBROOK, J . MOCHIDA, S . MONTECUCCO, C . NIEMANN, H. OGUMA,

K.

POPOFF,

M.

POULAIN,

B.

SIMPSON,

L.

SHONE, C . C. THommN,

D. E.

WELLER, U . WELLH6NER, WHELAN, S .

H. H. M.

225

Department of Biochemistry, The University of Edinburgh, Hugh Robson Building, George Square, GB-Edinburgh EH8 9XD, U.K . Department of Toxinology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, U.S.A. Department of Physiology, Tokyo Medical College, 1-1 Shinjuku-6-Chome, Shinjuku-Ku, Tokyo 160, Japan. Institute of General Pathology, University of Padua, Italy. Department of Microbiology, BFAV Tübingen, W-7400 Tübingen, F.R .G . Department of Microbiology, Sapporo Medical College, Sapporo 060, Japan. Institut Pasteur, Anaerobes, 28 Rue du Dr Roux, 75724 Paris, Cedex 15, France . Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, F91198 Gif-sur-Yvette Cedex, France. Division of Environmenatal Medicine and Toxicology, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA19107, U.S.A. Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire SP4 OJG, U.K. AFRC Institute of Food Research, Reading Laboratory, Shinfield, Reading RG2 9AT, U.K . Institute of Medical Microbiology, Hochhaus am Augustusplatz, W-6500 Mainz, F.R.G . Institute of Toxicology, Medical School of Hannover, W-3000 Hannover 61, F.R.G. Division of Biotechnology, PHLS Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire SP4 OJG, U.K .