Molecular mechanisms in the activation of abscisic acid receptor PYR1.

The pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory component of abscisic acid (ABA) response (RCAR) proteins comprise a well characterized family of ABA receptors. Recent investigations have revealed two subsets of these receptors that, in the absence of ABA, either form inactive homodime...

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Autores principales:	Lyudmyla Dorosh, Olesya A Kharenko, Nandhakishore Rajagopalan, Michele C Loewen, Maria Stepanova
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/20c8bb9b83c34a75a37b73e9945aaa2e
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spelling	oai:doaj.org-article:20c8bb9b83c34a75a37b73e9945aaa2e2021-11-18T05:52:03ZMolecular mechanisms in the activation of abscisic acid receptor PYR1.1553-734X1553-735810.1371/journal.pcbi.1003114https://doaj.org/article/20c8bb9b83c34a75a37b73e9945aaa2e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23825939/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory component of abscisic acid (ABA) response (RCAR) proteins comprise a well characterized family of ABA receptors. Recent investigations have revealed two subsets of these receptors that, in the absence of ABA, either form inactive homodimers (PYR1 and PYLs 1-3) or mediate basal inhibition of downstream target type 2C protein phosphatases (PP2Cs; PYLs 4-10) respectively in vitro. Addition of ABA has been shown to release the apo-homodimers yielding ABA-bound monomeric holo-receptors that can interact with PP2Cs; highlighting a competitive-interaction process. Interaction selectivity has been shown to be mediated by subtle structural variations of primary sequence and ligand binding effects. Now, the dynamical contributions of ligand binding on interaction selectivity are investigated through extensive molecular dynamics (MD) simulations of apo and holo-PYR1 in monomeric and dimeric form as well as in complex with a PP2C, homology to ABA insensitive 1 (HAB1). Robust comparative interpretations were enabled by a novel essential collective dynamics approach. In agreement with recent experimental findings, our analysis indicates that ABA-bound PYR1 should efficiently bind to HAB1. However, both ABA-bound and ABA-extracted PYR1-HAB1 constructs have demonstrated notable similarities in their dynamics, suggesting that apo-PYR1 should also be able to make a substantial interaction with PP2Cs, albeit likely with slower complex formation kinetics. Further analysis indicates that both ABA-bound and ABA-free PYR1 in complex with HAB1 exhibit a higher intra-molecular structural stability and stronger inter-molecular dynamic correlations, in comparison with either holo- or apo-PYR1 dimers, supporting a model that includes apo-PYR1 in complex with HAB1. This possibility of a conditional functional apo-PYR1-PP2C complex was validated in vitro. These findings are generally consistent with the competitive-interaction model for PYR1 but highlight dynamical contributions of the PYR1 structure in mediating interaction selectivity suggesting added degrees of complexity in the regulation of the competitive-inhibition.Lyudmyla DoroshOlesya A KharenkoNandhakishore RajagopalanMichele C LoewenMaria StepanovaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 6, p e1003114 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Lyudmyla Dorosh Olesya A Kharenko Nandhakishore Rajagopalan Michele C Loewen Maria Stepanova Molecular mechanisms in the activation of abscisic acid receptor PYR1.
description	The pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory component of abscisic acid (ABA) response (RCAR) proteins comprise a well characterized family of ABA receptors. Recent investigations have revealed two subsets of these receptors that, in the absence of ABA, either form inactive homodimers (PYR1 and PYLs 1-3) or mediate basal inhibition of downstream target type 2C protein phosphatases (PP2Cs; PYLs 4-10) respectively in vitro. Addition of ABA has been shown to release the apo-homodimers yielding ABA-bound monomeric holo-receptors that can interact with PP2Cs; highlighting a competitive-interaction process. Interaction selectivity has been shown to be mediated by subtle structural variations of primary sequence and ligand binding effects. Now, the dynamical contributions of ligand binding on interaction selectivity are investigated through extensive molecular dynamics (MD) simulations of apo and holo-PYR1 in monomeric and dimeric form as well as in complex with a PP2C, homology to ABA insensitive 1 (HAB1). Robust comparative interpretations were enabled by a novel essential collective dynamics approach. In agreement with recent experimental findings, our analysis indicates that ABA-bound PYR1 should efficiently bind to HAB1. However, both ABA-bound and ABA-extracted PYR1-HAB1 constructs have demonstrated notable similarities in their dynamics, suggesting that apo-PYR1 should also be able to make a substantial interaction with PP2Cs, albeit likely with slower complex formation kinetics. Further analysis indicates that both ABA-bound and ABA-free PYR1 in complex with HAB1 exhibit a higher intra-molecular structural stability and stronger inter-molecular dynamic correlations, in comparison with either holo- or apo-PYR1 dimers, supporting a model that includes apo-PYR1 in complex with HAB1. This possibility of a conditional functional apo-PYR1-PP2C complex was validated in vitro. These findings are generally consistent with the competitive-interaction model for PYR1 but highlight dynamical contributions of the PYR1 structure in mediating interaction selectivity suggesting added degrees of complexity in the regulation of the competitive-inhibition.
format	article
author	Lyudmyla Dorosh Olesya A Kharenko Nandhakishore Rajagopalan Michele C Loewen Maria Stepanova
author_facet	Lyudmyla Dorosh Olesya A Kharenko Nandhakishore Rajagopalan Michele C Loewen Maria Stepanova
author_sort	Lyudmyla Dorosh
title	Molecular mechanisms in the activation of abscisic acid receptor PYR1.
title_short	Molecular mechanisms in the activation of abscisic acid receptor PYR1.
title_full	Molecular mechanisms in the activation of abscisic acid receptor PYR1.
title_fullStr	Molecular mechanisms in the activation of abscisic acid receptor PYR1.
title_full_unstemmed	Molecular mechanisms in the activation of abscisic acid receptor PYR1.
title_sort	molecular mechanisms in the activation of abscisic acid receptor pyr1.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/20c8bb9b83c34a75a37b73e9945aaa2e
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Molecular mechanisms in the activation of abscisic acid receptor PYR1.

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