Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP

The transactivation domain (TAD) of tumor suppressor p53 can bind with the nuclear coactivator binding domain (NCBD) of cyclic-AMP response element binding protein (CBP) and activate transcription. NMR experiments demonstrate that both apo-NCBD and TAD are intrinsic disordered and bound NCBD/TAD und...

Full description

Bibliographic Details
Main Authors:	Yu, Qingfen, Ye, Wei, Wang, Wei, Chen, Hai-Feng
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608666/

id	pubmed-3608666
recordtype	oai_dc
spelling	pubmed-36086662013-04-03 Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP Yu, Qingfen Ye, Wei Wang, Wei Chen, Hai-Feng Research Article The transactivation domain (TAD) of tumor suppressor p53 can bind with the nuclear coactivator binding domain (NCBD) of cyclic-AMP response element binding protein (CBP) and activate transcription. NMR experiments demonstrate that both apo-NCBD and TAD are intrinsic disordered and bound NCBD/TAD undergoes a transition to well folded. The recognition mechanism between intrinsic disordered proteins is still hotly debated. Molecular dynamics (MD) simulations in explicit solvent are used to study the recognition mechanism between intrinsic disordered TAD and NCBD. The average RMSD values between bound and corresponding apo states and Kolmogorov-Smirnov P test analysis indicate that TAD and NCBD may follow an induced fit mechanism. Quantitative analysis indicates there is also a global conformational selection. In summary, the recognition of TAD and NCBD might obey a local induced fit and global conformational selection. These conclusions are further supported by high-temperature unbinding kinetics and room temperature landscape analysis. These methods can be used to study the recognition mechanism of other intrinsic disordered proteins. Public Library of Science 2013-03-26 /pmc/articles/PMC3608666/ /pubmed/23555731 http://dx.doi.org/10.1371/journal.pone.0059627 Text en © 2013 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yu, Qingfen Ye, Wei Wang, Wei Chen, Hai-Feng
spellingShingle	Yu, Qingfen Ye, Wei Wang, Wei Chen, Hai-Feng Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP
author_facet	Yu, Qingfen Ye, Wei Wang, Wei Chen, Hai-Feng
author_sort	Yu, Qingfen
title	Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP
title_short	Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP
title_full	Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP
title_fullStr	Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP
title_full_unstemmed	Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP
title_sort	global conformational selection and local induced fit for the recognition between intrinsic disordered p53 and cbp
description	The transactivation domain (TAD) of tumor suppressor p53 can bind with the nuclear coactivator binding domain (NCBD) of cyclic-AMP response element binding protein (CBP) and activate transcription. NMR experiments demonstrate that both apo-NCBD and TAD are intrinsic disordered and bound NCBD/TAD undergoes a transition to well folded. The recognition mechanism between intrinsic disordered proteins is still hotly debated. Molecular dynamics (MD) simulations in explicit solvent are used to study the recognition mechanism between intrinsic disordered TAD and NCBD. The average RMSD values between bound and corresponding apo states and Kolmogorov-Smirnov P test analysis indicate that TAD and NCBD may follow an induced fit mechanism. Quantitative analysis indicates there is also a global conformational selection. In summary, the recognition of TAD and NCBD might obey a local induced fit and global conformational selection. These conclusions are further supported by high-temperature unbinding kinetics and room temperature landscape analysis. These methods can be used to study the recognition mechanism of other intrinsic disordered proteins.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608666/
_version_	1611965520034136064

Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP

Similar Items