| Optimizing ring assembly reveals the strength of weak interactions. | |
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MedLine Citation:
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PMID: 22308356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Most cellular processes rely on large multiprotein complexes that must assemble into a well-defined quaternary structure in order to function. A number of prominent examples, including the 20S core particle of the proteasome and the AAA+ family of ATPases, contain ring-like structures. Developing an understanding of the complex assembly pathways employed by ring-like structures requires a characterization of the problems these pathways have had to overcome as they evolved. In this work, we use computational models to uncover one such problem: a deadlocked plateau in the assembly dynamics. When the molecular interactions between subunits are too strong, this plateau leads to significant delays in assembly and a reduction in steady-state yield. Conversely, if the interactions are too weak, assembly delays are caused by the instability of crucial intermediates. Intermediate affinities thus maximize the efficiency of assembly for homomeric ring-like structures. In the case of heteromeric rings, we find that rings including at least one weak interaction can assemble efficiently and robustly. Estimation of affinities from solved structures of ring-like complexes indicates that heteromeric rings tend to contain a weak interaction, confirming our prediction. In addition to providing an evolutionary rationale for structural features of rings, our work forms the basis for understanding the complex assembly pathways of stacked rings like the proteasome and suggests principles that would aid in the design of synthetic ring-like structures that self-assemble efficiently. |
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Authors:
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Eric J Deeds; John A Bachman; Walter Fontana |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-01-30 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 109 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-15 Completed Date: 2012-04-20 Revised Date: 2012-09-26 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 2348-53 Citation Subset: IM |
Affiliation:
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Center for Bioinformatics and Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66047, USA. deeds@ku.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Models, Molecular Protein Binding* Protein Conformation |
| Comments/Corrections | |
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