Conformational dynamics of capping protein and interaction partners : simulation studies

Capping protein (CP) is important for the regulation of actin polymerization. CP binds to the barbed end of the actin filament and prevents actin polymerization. This interaction is modulated through competitive binding by regulatory proteins such as myotrophin (V-1) and the capping protein interact...

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Main Authors: Wales, David., Verma, Chandra S., Lukman, Suryani., Robinson, Robert C.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/97996
http://hdl.handle.net/10220/12220
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-979962020-03-07T12:18:18Z Conformational dynamics of capping protein and interaction partners : simulation studies Wales, David. Verma, Chandra S. Lukman, Suryani. Robinson, Robert C. School of Biological Sciences DRNTU::Science::Biological sciences Capping protein (CP) is important for the regulation of actin polymerization. CP binds to the barbed end of the actin filament and prevents actin polymerization. This interaction is modulated through competitive binding by regulatory proteins such as myotrophin (V-1) and the capping protein interacting (CPI) motif from CARMIL. The binding site of myotrophin overlaps with the region of CP that binds to the barbed end of actin filament, whereas CPI binds at a distant site. The binding of CPI to the myotrophin-CP complex dissociates myotrophin from CP. Detailed multicopy molecular dynamics simulations suggest that the binding of CPI shifts the conformational equilibria of CP away from states that favor myotrophin binding. This shift is underpinned by allosteric effects where CPI inhibits CP through suppression of flexibility and disruption of concerted motions that appear to mediate myotrophin binding. Accompanying these effects are changes in electrostatic interactions, notably those involving residue K142β, which appears to play a critical role in regulating flexibility. In addition, accessibility of the site on CP for binding the key hydrophobic residue W8 of myotrophin is modulated by CPI. These results provide insights into the modulation of CP by CPI and myotrophin and indicate the mechanism by which CPI drives the dissociation of the myotrophin-CP complex. Proteins 2012;. © 2011 Wiley Periodicals, Inc. 2013-07-25T05:56:46Z 2019-12-06T19:49:09Z 2013-07-25T05:56:46Z 2019-12-06T19:49:09Z 2011 2011 Journal Article Lukman, S., Robinson, R. C., Wales, D., & Verma, C. S. (2012). Conformational dynamics of capping protein and interaction partners: Simulation studies. Proteins: Structure, Function, and Bioinformatics, 80(4), 1066-1077. 0887-3585 https://hdl.handle.net/10356/97996 http://hdl.handle.net/10220/12220 10.1002/prot.24008 en Proteins: structure, function, and bioinformatics © 2011 Wiley Periodicals, Inc.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Wales, David.
Verma, Chandra S.
Lukman, Suryani.
Robinson, Robert C.
Conformational dynamics of capping protein and interaction partners : simulation studies
description Capping protein (CP) is important for the regulation of actin polymerization. CP binds to the barbed end of the actin filament and prevents actin polymerization. This interaction is modulated through competitive binding by regulatory proteins such as myotrophin (V-1) and the capping protein interacting (CPI) motif from CARMIL. The binding site of myotrophin overlaps with the region of CP that binds to the barbed end of actin filament, whereas CPI binds at a distant site. The binding of CPI to the myotrophin-CP complex dissociates myotrophin from CP. Detailed multicopy molecular dynamics simulations suggest that the binding of CPI shifts the conformational equilibria of CP away from states that favor myotrophin binding. This shift is underpinned by allosteric effects where CPI inhibits CP through suppression of flexibility and disruption of concerted motions that appear to mediate myotrophin binding. Accompanying these effects are changes in electrostatic interactions, notably those involving residue K142β, which appears to play a critical role in regulating flexibility. In addition, accessibility of the site on CP for binding the key hydrophobic residue W8 of myotrophin is modulated by CPI. These results provide insights into the modulation of CP by CPI and myotrophin and indicate the mechanism by which CPI drives the dissociation of the myotrophin-CP complex. Proteins 2012;. © 2011 Wiley Periodicals, Inc.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Wales, David.
Verma, Chandra S.
Lukman, Suryani.
Robinson, Robert C.
format Article
author Wales, David.
Verma, Chandra S.
Lukman, Suryani.
Robinson, Robert C.
author_sort Wales, David.
title Conformational dynamics of capping protein and interaction partners : simulation studies
title_short Conformational dynamics of capping protein and interaction partners : simulation studies
title_full Conformational dynamics of capping protein and interaction partners : simulation studies
title_fullStr Conformational dynamics of capping protein and interaction partners : simulation studies
title_full_unstemmed Conformational dynamics of capping protein and interaction partners : simulation studies
title_sort conformational dynamics of capping protein and interaction partners : simulation studies
publishDate 2013
url https://hdl.handle.net/10356/97996
http://hdl.handle.net/10220/12220
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