Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization

The conformational plasticity of serpins underlies both their activities as protease inhibitors and their susceptibility to pathogenic misfolding. Here, we structurally characterize a sheet-opened state of the serpin alpha-1 antitrypsin (α(1)AT) and show how local unfolding allows functionally essen...

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Autores principales: Krishnan, Beena, Gierasch, Lila M.
Formato: Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074950/
https://www.ncbi.nlm.nih.gov/pubmed/21258324
http://dx.doi.org/10.1038/nsmb.1976
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author Krishnan, Beena
Gierasch, Lila M.
author_facet Krishnan, Beena
Gierasch, Lila M.
author_sort Krishnan, Beena
collection PubMed
description The conformational plasticity of serpins underlies both their activities as protease inhibitors and their susceptibility to pathogenic misfolding. Here, we structurally characterize a sheet-opened state of the serpin alpha-1 antitrypsin (α(1)AT) and show how local unfolding allows functionally essential strand insertion. Mutations in α(1)AT that cause polymerization-induced serpinopathies map to the labile region, suggesting that the evolution of serpin function required them to sample conformations on a dynamic energy landscape that increased risk of aggregation.
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spelling pubmed-30749502011-08-01 Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization Krishnan, Beena Gierasch, Lila M. Nat Struct Mol Biol Article The conformational plasticity of serpins underlies both their activities as protease inhibitors and their susceptibility to pathogenic misfolding. Here, we structurally characterize a sheet-opened state of the serpin alpha-1 antitrypsin (α(1)AT) and show how local unfolding allows functionally essential strand insertion. Mutations in α(1)AT that cause polymerization-induced serpinopathies map to the labile region, suggesting that the evolution of serpin function required them to sample conformations on a dynamic energy landscape that increased risk of aggregation. 2011-01-23 2011-02 /pmc/articles/PMC3074950/ /pubmed/21258324 http://dx.doi.org/10.1038/nsmb.1976 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Krishnan, Beena
Gierasch, Lila M.
Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization
title Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization
title_full Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization
title_fullStr Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization
title_full_unstemmed Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization
title_short Dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization
title_sort dynamic local unfolding in the serpinalpha-1 antitrypsin provides a mechanism for loop insertion and polymerization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074950/
https://www.ncbi.nlm.nih.gov/pubmed/21258324
http://dx.doi.org/10.1038/nsmb.1976
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