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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: Dorosh, Lyudmyla, Kharenko, Olesya A., Rajagopalan, Nandhakishore, Loewen, Michele C., Stepanova, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694813/
https://www.ncbi.nlm.nih.gov/pubmed/23825939
http://dx.doi.org/10.1371/journal.pcbi.1003114
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author Dorosh, Lyudmyla
Kharenko, Olesya A.
Rajagopalan, Nandhakishore
Loewen, Michele C.
Stepanova, Maria
author_facet Dorosh, Lyudmyla
Kharenko, Olesya A.
Rajagopalan, Nandhakishore
Loewen, Michele C.
Stepanova, Maria
author_sort Dorosh, Lyudmyla
collection PubMed
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.
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spelling pubmed-36948132013-07-03 Molecular Mechanisms in the Activation of Abscisic Acid Receptor PYR1 Dorosh, Lyudmyla Kharenko, Olesya A. Rajagopalan, Nandhakishore Loewen, Michele C. Stepanova, Maria PLoS Comput Biol Research Article 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. Public Library of Science 2013-06-27 /pmc/articles/PMC3694813/ /pubmed/23825939 http://dx.doi.org/10.1371/journal.pcbi.1003114 Text en © 2013 Dorosh 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.
spellingShingle Research Article
Dorosh, Lyudmyla
Kharenko, Olesya A.
Rajagopalan, Nandhakishore
Loewen, Michele C.
Stepanova, Maria
Molecular Mechanisms in the Activation of Abscisic Acid Receptor PYR1
title 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_short Molecular Mechanisms in the Activation of Abscisic Acid Receptor PYR1
title_sort molecular mechanisms in the activation of abscisic acid receptor pyr1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694813/
https://www.ncbi.nlm.nih.gov/pubmed/23825939
http://dx.doi.org/10.1371/journal.pcbi.1003114
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