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Protein folding and misfolding

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  • Christopher M. Dobson

    (University of Cambridge)

Abstract

The manner in which a newly synthesized chain of amino acids transforms itself into a perfectly folded protein depends both on the intrinsic properties of the amino-acid sequence and on multiple contributing influences from the crowded cellular milieu. Folding and unfolding are crucial ways of regulating biological activity and targeting proteins to different cellular locations. Aggregation of misfolded proteins that escape the cellular quality-control mechanisms is a common feature of a wide range of highly debilitating and increasingly prevalent diseases.

Suggested Citation

  • Christopher M. Dobson, 2003. "Protein folding and misfolding," Nature, Nature, vol. 426(6968), pages 884-890, December.
    • Handle: RePEc:nat:nature:v:426:y:2003:i:6968:d:10.1038_nature02261
    DOI: 10.1038/nature02261
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    Citations

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    Cited by:

    1. Espinoza Ortiz, J.S. & Dias, Cristiano L., 2018. "Cooperative fibril model: Native, amyloid-like fibril and unfolded states of proteins," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 511(C), pages 154-165.
    2. Qi Wang & Joshua L Johnson & Nathalie YR Agar & Jeffrey N Agar, 2008. "Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival," PLOS Biology, Public Library of Science, vol. 6(7), pages 1-19, July.
    3. Minkoo Ahn & Tomasz Włodarski & Alkistis Mitropoulou & Sammy H. S. Chan & Haneesh Sidhu & Elena Plessa & Thomas A. Becker & Nediljko Budisa & Christopher A. Waudby & Roland Beckmann & Anaïs M. E. Cass, 2022. "Modulating co-translational protein folding by rational design and ribosome engineering," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Guosheng Chen & Linjing Tong & Siming Huang & Shuyao Huang & Fang Zhu & Gangfeng Ouyang, 2022. "Hydrogen-bonded organic framework biomimetic entrapment allowing non-native biocatalytic activity in enzyme," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Pengfei Tian & Kresten Lindorff-Larsen & Wouter Boomsma & Mogens Høgh Jensen & Daniel Erik Otzen, 2016. "A Monte Carlo Study of the Early Steps of Functional Amyloid Formation," PLOS ONE, Public Library of Science, vol. 11(1), pages 1-18, January.
    6. Mookyung Cheon & Iksoo Chang & Sandipan Mohanty & Leila M Luheshi & Christopher M Dobson & Michele Vendruscolo & Giorgio Favrin, 2007. "Structural Reorganisation and Potential Toxicity of Oligomeric Species Formed during the Assembly of Amyloid Fibrils," PLOS Computational Biology, Public Library of Science, vol. 3(9), pages 1-12, September.
    7. Arthur Fischbach & Angela Johns & Kara L. Schneider & Xinxin Hao & Peter Tessarz & Thomas Nyström, 2023. "Artificial Hsp104-mediated systems for re-localizing protein aggregates," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Jian Tian & Jaie C Woodard & Anna Whitney & Eugene I Shakhnovich, 2015. "Thermal Stabilization of Dihydrofolate Reductase Using Monte Carlo Unfolding Simulations and Its Functional Consequences," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-27, April.
    9. Wen-Ting Chu & Ji-Long Zhang & Qing-Chuan Zheng & Lin Chen & Hong-Xing Zhang, 2013. "Insights into the Folding and Unfolding Processes of Wild-Type and Mutated SH3 Domain by Molecular Dynamics and Replica Exchange Molecular Dynamics Simulations," PLOS ONE, Public Library of Science, vol. 8(5), pages 1-9, May.
    10. Noah S Bieler & Tuomas P J Knowles & Daan Frenkel & Robert Vácha, 2012. "Connecting Macroscopic Observables and Microscopic Assembly Events in Amyloid Formation Using Coarse Grained Simulations," PLOS Computational Biology, Public Library of Science, vol. 8(10), pages 1-10, October.
    11. Allen W Bryan Jr. & Matthew Menke & Lenore J Cowen & Susan L Lindquist & Bonnie Berger, 2009. "BETASCAN: Probable β-amyloids Identified by Pairwise Probabilistic Analysis," PLOS Computational Biology, Public Library of Science, vol. 5(3), pages 1-11, March.
    12. Kübra Kaygisiz & Lena Rauch-Wirth & Arghya Dutta & Xiaoqing Yu & Yuki Nagata & Tristan Bereau & Jan Münch & Christopher V. Synatschke & Tanja Weil, 2023. "Data-mining unveils structure–property–activity correlation of viral infectivity enhancing self-assembling peptides," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Jaya C Jose & Prathit Chatterjee & Neelanjana Sengupta, 2014. "Cross Dimerization of Amyloid-β and αSynuclein Proteins in Aqueous Environment: A Molecular Dynamics Simulations Study," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-13, September.
    14. Matthias M. Schneider & Saurabh Gautam & Therese W. Herling & Ewa Andrzejewska & Georg Krainer & Alyssa M. Miller & Victoria A. Trinkaus & Quentin A. E. Peter & Francesco Simone Ruggeri & Michele Vend, 2021. "The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    15. Sanne Abeln & Michele Vendruscolo & Christopher M Dobson & Daan Frenkel, 2014. "A Simple Lattice Model That Captures Protein Folding, Aggregation and Amyloid Formation," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-8, January.
    16. Morten S Dueholm & Daniel Otzen & Per Halkjær Nielsen, 2013. "Evolutionary Insight into the Functional Amyloids of the Pseudomonads," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-1, October.
    17. Eri Chatani & Yutaro Tsuchisaka & Yuki Masuda & Roumiana Tsenkova, 2014. "Water Molecular System Dynamics Associated with Amyloidogenic Nucleation as Revealed by Real Time Near Infrared Spectroscopy and Aquaphotomics," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-10, July.
    18. Carlos Família & Sarah R Dennison & Alexandre Quintas & David A Phoenix, 2015. "Prediction of Peptide and Protein Propensity for Amyloid Formation," PLOS ONE, Public Library of Science, vol. 10(8), pages 1-16, August.
    19. Sheng Chen & Anuradhika Puri & Braxton Bell & Joseph Fritsche & Hector H. Palacios & Maurie Balch & Macy L. Sprunger & Matthew K. Howard & Jeremy J. Ryan & Jessica N. Haines & Gary J. Patti & Albert A, 2024. "HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    20. Bente Vestergaard & Minna Groenning & Manfred Roessle & Jette S Kastrup & Marco van de Weert & James M Flink & Sven Frokjaer & Michael Gajhede & Dmitri I Svergun, 2007. "A Helical Structural Nucleus Is the Primary Elongating Unit of Insulin Amyloid Fibrils," PLOS Biology, Public Library of Science, vol. 5(5), pages 1-9, May.
    21. Morten S Dueholm & Mads Albertsen & Daniel Otzen & Per Halkjær Nielsen, 2012. "Curli Functional Amyloid Systems Are Phylogenetically Widespread and Display Large Diversity in Operon and Protein Structure," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-10, December.
    22. Corina N. D’Alessandro-Gabazza & Taro Yasuma & Tetsu Kobayashi & Masaaki Toda & Ahmed M. Abdel-Hamid & Hajime Fujimoto & Osamu Hataji & Hiroki Nakahara & Atsuro Takeshita & Kota Nishihama & Tomohito O, 2022. "Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    23. Stefan Auer & Filip Meersman & Christopher M Dobson & Michele Vendruscolo, 2008. "A Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric Aggregates," PLOS Computational Biology, Public Library of Science, vol. 4(11), pages 1-7, November.

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