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Evolution of interface binding strengths in simplified model of protein quaternary structure

The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate t...

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Autores principales: Leonard, Alexander S., Ahnert, Sebastian E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6564041/
https://www.ncbi.nlm.nih.gov/pubmed/31158218
http://dx.doi.org/10.1371/journal.pcbi.1006886
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author Leonard, Alexander S.
Ahnert, Sebastian E.
author_facet Leonard, Alexander S.
Ahnert, Sebastian E.
author_sort Leonard, Alexander S.
collection PubMed
description The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new idealized framework to facilitate the study of protein self-assembly processes and their evolution.
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spelling pubmed-65640412019-06-20 Evolution of interface binding strengths in simplified model of protein quaternary structure Leonard, Alexander S. Ahnert, Sebastian E. PLoS Comput Biol Research Article The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new idealized framework to facilitate the study of protein self-assembly processes and their evolution. Public Library of Science 2019-06-03 /pmc/articles/PMC6564041/ /pubmed/31158218 http://dx.doi.org/10.1371/journal.pcbi.1006886 Text en © 2019 Leonard, Ahnert http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Leonard, Alexander S.
Ahnert, Sebastian E.
Evolution of interface binding strengths in simplified model of protein quaternary structure
title Evolution of interface binding strengths in simplified model of protein quaternary structure
title_full Evolution of interface binding strengths in simplified model of protein quaternary structure
title_fullStr Evolution of interface binding strengths in simplified model of protein quaternary structure
title_full_unstemmed Evolution of interface binding strengths in simplified model of protein quaternary structure
title_short Evolution of interface binding strengths in simplified model of protein quaternary structure
title_sort evolution of interface binding strengths in simplified model of protein quaternary structure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6564041/
https://www.ncbi.nlm.nih.gov/pubmed/31158218
http://dx.doi.org/10.1371/journal.pcbi.1006886
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