The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.

The C-terminal V5 domain is one of the most variable domains in Protein Kinase C isoforms (PKCs). V5 confers isoform specificity on its parent enzyme through interactions with isoform-specific adaptor proteins and possibly through specific intra-molecular interactions with other PKC domains. The str...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yuan Yang, Tatyana I Igumenova
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f9c4879a3b15454a925904876666e02a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f9c4879a3b15454a925904876666e02a
record_format	dspace
spelling	oai:doaj.org-article:f9c4879a3b15454a925904876666e02a2021-11-18T07:42:44ZThe C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.1932-620310.1371/journal.pone.0065699https://doaj.org/article/f9c4879a3b15454a925904876666e02a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762412/?tool=EBIhttps://doaj.org/toc/1932-6203The C-terminal V5 domain is one of the most variable domains in Protein Kinase C isoforms (PKCs). V5 confers isoform specificity on its parent enzyme through interactions with isoform-specific adaptor proteins and possibly through specific intra-molecular interactions with other PKC domains. The structural information about V5 domains in solution is sparse. The objective of this work was to determine the conformational preferences of the V5 domain from the α isoform of PKC (V5α) and evaluate its ability to associate with membrane mimetics. We show that V5α and its phosphorylation-mimicking variant, dmV5α, are intrinsically disordered protein domains. Phosphorylation-mimicking mutations do not alter the overall conformation of the polypeptide backbone, as evidenced by the local nature of chemical shift perturbations and the secondary structure propensity scores. However, the population of the "cis-trans" conformer of the Thr(638)-Pro(639)-Pro(640) turn motif, which has been implicated in the down-regulation of PKCα via peptidyl-prolyl isomerase Pin1, increases in dmV5α, along with the conformational flexibility of the region between the turn and hydrophobic motifs. Both wild type and dmV5α associate with micelles made of a zwitterionic detergent, n-dodecylphosphocholine. Upon micelle binding, V5α acquires a higher propensity to form helical structures at the conserved "NFD" motif and the entire C-terminal third of the domain. The ability of V5α to partition into the hydrophobic micellar environment suggests that it may serve as a membrane anchor during the PKC maturation process.Yuan YangTatyana I IgumenovaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65699 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuan Yang Tatyana I Igumenova The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.
description	The C-terminal V5 domain is one of the most variable domains in Protein Kinase C isoforms (PKCs). V5 confers isoform specificity on its parent enzyme through interactions with isoform-specific adaptor proteins and possibly through specific intra-molecular interactions with other PKC domains. The structural information about V5 domains in solution is sparse. The objective of this work was to determine the conformational preferences of the V5 domain from the α isoform of PKC (V5α) and evaluate its ability to associate with membrane mimetics. We show that V5α and its phosphorylation-mimicking variant, dmV5α, are intrinsically disordered protein domains. Phosphorylation-mimicking mutations do not alter the overall conformation of the polypeptide backbone, as evidenced by the local nature of chemical shift perturbations and the secondary structure propensity scores. However, the population of the "cis-trans" conformer of the Thr(638)-Pro(639)-Pro(640) turn motif, which has been implicated in the down-regulation of PKCα via peptidyl-prolyl isomerase Pin1, increases in dmV5α, along with the conformational flexibility of the region between the turn and hydrophobic motifs. Both wild type and dmV5α associate with micelles made of a zwitterionic detergent, n-dodecylphosphocholine. Upon micelle binding, V5α acquires a higher propensity to form helical structures at the conserved "NFD" motif and the entire C-terminal third of the domain. The ability of V5α to partition into the hydrophobic micellar environment suggests that it may serve as a membrane anchor during the PKC maturation process.
format	article
author	Yuan Yang Tatyana I Igumenova
author_facet	Yuan Yang Tatyana I Igumenova
author_sort	Yuan Yang
title	The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.
title_short	The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.
title_full	The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.
title_fullStr	The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.
title_full_unstemmed	The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.
title_sort	c-terminal v5 domain of protein kinase cα is intrinsically disordered, with propensity to associate with a membrane mimetic.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f9c4879a3b15454a925904876666e02a
work_keys_str_mv	AT yuanyang thecterminalv5domainofproteinkinasecaisintrinsicallydisorderedwithpropensitytoassociatewithamembranemimetic AT tatyanaiigumenova thecterminalv5domainofproteinkinasecaisintrinsicallydisorderedwithpropensitytoassociatewithamembranemimetic AT yuanyang cterminalv5domainofproteinkinasecaisintrinsicallydisorderedwithpropensitytoassociatewithamembranemimetic AT tatyanaiigumenova cterminalv5domainofproteinkinasecaisintrinsicallydisorderedwithpropensitytoassociatewithamembranemimetic
_version_	1718423137246248960

The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.

Ejemplares similares