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F–actin-bundling sites are conserved in proteins with villin-type headpiece domains

Villin is a major actin-bundling protein that assembles the brush border of intestinal and renal epithelial cells. The villin “headpiece” domain and the actin-binding residues within it regulate its actin-bundling function. Substantial experimental and theoretical information about the three-dimensi...

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Autores principales: George, Sudeep P., Esmaeilniakooshkghazi, Amin, Roy, Swati, Khurana, Seema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525818/
https://www.ncbi.nlm.nih.gov/pubmed/32520642
http://dx.doi.org/10.1091/mbc.E20-02-0158
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author George, Sudeep P.
Esmaeilniakooshkghazi, Amin
Roy, Swati
Khurana, Seema
author_facet George, Sudeep P.
Esmaeilniakooshkghazi, Amin
Roy, Swati
Khurana, Seema
author_sort George, Sudeep P.
collection PubMed
description Villin is a major actin-bundling protein that assembles the brush border of intestinal and renal epithelial cells. The villin “headpiece” domain and the actin-binding residues within it regulate its actin-bundling function. Substantial experimental and theoretical information about the three-dimensional structure of the isolated villin headpiece, including a description of the actin-binding residues within the headpiece, is available. Despite that, the actin-bundling site in the full-length (FL) villin protein remains unidentified. We used this existing villin headpiece nuclear magnetic resonance data and performed mutational analysis and functional assays to identify the actin-bundling site in FL human villin protein. By careful evaluation of these conserved actin-binding residues in human advillin protein, we demonstrate their functional significance in the over 30 proteins that contain a villin-type headpiece domain. Our study is the first that combines the available structural data on villin headpiece with functional assays to identify the actin-binding residues in FL villin that regulate its filament-bundling activity. Our findings could have wider implications for other actin-bundling proteins that contain a villin-type headpiece domain.
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spelling pubmed-75258182020-10-16 F–actin-bundling sites are conserved in proteins with villin-type headpiece domains George, Sudeep P. Esmaeilniakooshkghazi, Amin Roy, Swati Khurana, Seema Mol Biol Cell Brief Reports Villin is a major actin-bundling protein that assembles the brush border of intestinal and renal epithelial cells. The villin “headpiece” domain and the actin-binding residues within it regulate its actin-bundling function. Substantial experimental and theoretical information about the three-dimensional structure of the isolated villin headpiece, including a description of the actin-binding residues within the headpiece, is available. Despite that, the actin-bundling site in the full-length (FL) villin protein remains unidentified. We used this existing villin headpiece nuclear magnetic resonance data and performed mutational analysis and functional assays to identify the actin-bundling site in FL human villin protein. By careful evaluation of these conserved actin-binding residues in human advillin protein, we demonstrate their functional significance in the over 30 proteins that contain a villin-type headpiece domain. Our study is the first that combines the available structural data on villin headpiece with functional assays to identify the actin-binding residues in FL villin that regulate its filament-bundling activity. Our findings could have wider implications for other actin-bundling proteins that contain a villin-type headpiece domain. The American Society for Cell Biology 2020-08-01 /pmc/articles/PMC7525818/ /pubmed/32520642 http://dx.doi.org/10.1091/mbc.E20-02-0158 Text en © 2020 George et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Brief Reports
George, Sudeep P.
Esmaeilniakooshkghazi, Amin
Roy, Swati
Khurana, Seema
F–actin-bundling sites are conserved in proteins with villin-type headpiece domains
title F–actin-bundling sites are conserved in proteins with villin-type headpiece domains
title_full F–actin-bundling sites are conserved in proteins with villin-type headpiece domains
title_fullStr F–actin-bundling sites are conserved in proteins with villin-type headpiece domains
title_full_unstemmed F–actin-bundling sites are conserved in proteins with villin-type headpiece domains
title_short F–actin-bundling sites are conserved in proteins with villin-type headpiece domains
title_sort f–actin-bundling sites are conserved in proteins with villin-type headpiece domains
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525818/
https://www.ncbi.nlm.nih.gov/pubmed/32520642
http://dx.doi.org/10.1091/mbc.E20-02-0158
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