BB43CH17-Shan
ARI
19 May 2014
ANNUAL REVIEWS
16:31
Further
Annu. Rev. Biophys. 2014.43:381-408. Downloaded from www.annualreviews.org Access provided by University of Utah - Marriot Library on 11/30/14. For personal use only.
Click here for quick links to Annual Reviews content online, including: • Other articles in this volume • Top cited articles • Top downloaded articles • Our comprehensive search
Fidelity of Cotranslational Protein Targeting by the Signal Recognition Particle Xin Zhang1,2 and Shu-ou Shan1 1 Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125; email: [email protected] 2 Current address: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037
Annu. Rev. Biophys. 2014. 43:381–408
Keywords
The Annual Review of Biophysics is online at biophys.annualreviews.org
protein biogenesis, signal sequence, GTPases, RNA, ribosome, protein translocation
This article’s doi: 10.1146/annurev-biophys-051013-022653 c 2014 by Annual Reviews. Copyright All rights reserved
Abstract Accurate folding, assembly, localization, and maturation of newly synthesized proteins are essential to all cells and require high fidelity in the protein biogenesis machineries that mediate these processes. Here, we review our current understanding of how high fidelity is achieved in one of these processes, the cotranslational targeting of nascent membrane and secretory proteins by the signal recognition particle (SRP). Recent biochemical, biophysical, and structural studies have elucidated how the correct substrates drive a series of elaborate conformational rearrangements in the SRP and SRP receptor GTPases; these rearrangements provide effective fidelity checkpoints to reject incorrect substrates and enhance the fidelity of this essential cellular pathway. The mechanisms used by SRP to ensure fidelity share important conceptual analogies with those used by cellular machineries involved in DNA replication, transcription, and translation, and these mechanisms likely represent general principles for other complex cellular pathways.
381
BB43CH17-Shan
ARI
19 May 2014
16:31
Contents
Annu. Rev. Biophys. 2014.43:381-408. Downloaded from www.annualreviews.org Access provided by University of Utah - Marriot Library on 11/30/14. For personal use only.
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . FIDELITY CONSIDERATIONS DURING PROTEIN BIOGENESIS . . . . . . . . . . . Multiplicity of Fates During the Biogenesis of Nascent Proteins . . . . . . . . . . . . . . . . . . Fidelity in Protein Localization: General Principles and Challenges . . . . . . . . . . . . . . . SEQUENTIAL CHECKPOINTS GOVERN THE FIDELITY OF COTRANSLATIONAL PROTEIN TARGETING. . . . . . . . . . . . . . . . . . . . . . . . . Overview of the Signal Recognition Particle: Composition and Interaction Partners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cargo Recognition by the Signal Recognition Particle Is Insufficient to Ensure Fidelity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A Novel GTPase Cycle for the Signal Recognition Particle and Signal Recognition Particle Receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Correct Cargos Drive Rapid Assembly of the Signal Recognition Particle (SRP)–SRP Receptor GTPase Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Kinetic Proofreading Through GTP Hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Multiple Fidelity Checkpoints Govern Substrate Selection by the Signal Recognition Particle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . STRUCTURAL AND MOLECULAR BASIS OF FIDELITY CONTROL . . . . . . . . The Signal Recognition Particle RNA Mediates Substrate-Induced Reorganization of the Signal Recognition Particle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GTPase Movement to the RNA Distal End Activates GTP Hydrolysis . . . . . . . . . . . . PERSPECTIVE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
382 383 383 385 386 386 387 389 391 391 395 395 396 398 399
INTRODUCTION Generation of order and organization is an essential feature of life. Central to the establishment of this organization is the exquisite fidelity of biochemical reactions that mediate every aspect of biology. Efforts to understand mechanisms that give rise to biological fidelity began over half a century ago, in consideration of the accuracy with which genetic information is replicated and decoded. Although the initial hypothesis suggested that base-pairing interactions can provide selectivity, subsequent studies have indicated that the free energy differences between matched and mismatched base pairs are too small to account for the fidelity required to maintain genome integrity and far below the observed accuracy of the cellular machineries that mediate these processes. For example, the error rates of base-pairing interactions in solution are typically 10−3 – 10−4 , whereas DNA and RNA polymerases exhibit error rates of 10−6 –10−8 and 10−5 , respectively. The error rates of amino acid recognition by transfer RNA (tRNA) synthetases are on the order of 10−2 , whereas the translation process exhibits error rates of
ARI
19 May 2014
ANNUAL REVIEWS
16:31
Further
Annu. Rev. Biophys. 2014.43:381-408. Downloaded from www.annualreviews.org Access provided by University of Utah - Marriot Library on 11/30/14. For personal use only.
Click here for quick links to Annual Reviews content online, including: • Other articles in this volume • Top cited articles • Top downloaded articles • Our comprehensive search
Fidelity of Cotranslational Protein Targeting by the Signal Recognition Particle Xin Zhang1,2 and Shu-ou Shan1 1 Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125; email: [email protected] 2 Current address: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037
Annu. Rev. Biophys. 2014. 43:381–408
Keywords
The Annual Review of Biophysics is online at biophys.annualreviews.org
protein biogenesis, signal sequence, GTPases, RNA, ribosome, protein translocation
This article’s doi: 10.1146/annurev-biophys-051013-022653 c 2014 by Annual Reviews. Copyright All rights reserved
Abstract Accurate folding, assembly, localization, and maturation of newly synthesized proteins are essential to all cells and require high fidelity in the protein biogenesis machineries that mediate these processes. Here, we review our current understanding of how high fidelity is achieved in one of these processes, the cotranslational targeting of nascent membrane and secretory proteins by the signal recognition particle (SRP). Recent biochemical, biophysical, and structural studies have elucidated how the correct substrates drive a series of elaborate conformational rearrangements in the SRP and SRP receptor GTPases; these rearrangements provide effective fidelity checkpoints to reject incorrect substrates and enhance the fidelity of this essential cellular pathway. The mechanisms used by SRP to ensure fidelity share important conceptual analogies with those used by cellular machineries involved in DNA replication, transcription, and translation, and these mechanisms likely represent general principles for other complex cellular pathways.
381
BB43CH17-Shan
ARI
19 May 2014
16:31
Contents
Annu. Rev. Biophys. 2014.43:381-408. Downloaded from www.annualreviews.org Access provided by University of Utah - Marriot Library on 11/30/14. For personal use only.
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . FIDELITY CONSIDERATIONS DURING PROTEIN BIOGENESIS . . . . . . . . . . . Multiplicity of Fates During the Biogenesis of Nascent Proteins . . . . . . . . . . . . . . . . . . Fidelity in Protein Localization: General Principles and Challenges . . . . . . . . . . . . . . . SEQUENTIAL CHECKPOINTS GOVERN THE FIDELITY OF COTRANSLATIONAL PROTEIN TARGETING. . . . . . . . . . . . . . . . . . . . . . . . . Overview of the Signal Recognition Particle: Composition and Interaction Partners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cargo Recognition by the Signal Recognition Particle Is Insufficient to Ensure Fidelity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A Novel GTPase Cycle for the Signal Recognition Particle and Signal Recognition Particle Receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Correct Cargos Drive Rapid Assembly of the Signal Recognition Particle (SRP)–SRP Receptor GTPase Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Kinetic Proofreading Through GTP Hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Multiple Fidelity Checkpoints Govern Substrate Selection by the Signal Recognition Particle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . STRUCTURAL AND MOLECULAR BASIS OF FIDELITY CONTROL . . . . . . . . The Signal Recognition Particle RNA Mediates Substrate-Induced Reorganization of the Signal Recognition Particle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GTPase Movement to the RNA Distal End Activates GTP Hydrolysis . . . . . . . . . . . . PERSPECTIVE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
382 383 383 385 386 386 387 389 391 391 395 395 396 398 399
INTRODUCTION Generation of order and organization is an essential feature of life. Central to the establishment of this organization is the exquisite fidelity of biochemical reactions that mediate every aspect of biology. Efforts to understand mechanisms that give rise to biological fidelity began over half a century ago, in consideration of the accuracy with which genetic information is replicated and decoded. Although the initial hypothesis suggested that base-pairing interactions can provide selectivity, subsequent studies have indicated that the free energy differences between matched and mismatched base pairs are too small to account for the fidelity required to maintain genome integrity and far below the observed accuracy of the cellular machineries that mediate these processes. For example, the error rates of base-pairing interactions in solution are typically 10−3 – 10−4 , whereas DNA and RNA polymerases exhibit error rates of 10−6 –10−8 and 10−5 , respectively. The error rates of amino acid recognition by transfer RNA (tRNA) synthetases are on the order of 10−2 , whereas the translation process exhibits error rates of
