The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins

Abstract We recently found that nuclear receptor coactivator 7 (Ncoa7) and Oxr1 interact with the proton-pumping V-ATPase. Ncoa7 and Oxr1 belong to a group of proteins playing a role in the oxidative stress response, that contain the conserved “TLDc” domain. Here we asked if the three other proteins...

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Autores principales:	A. F. Eaton, D. Brown, M. Merkulova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5fd2824740524c3bbbaccdbeb52a3e10
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spelling	oai:doaj.org-article:5fd2824740524c3bbbaccdbeb52a3e102021-11-28T12:21:26ZThe evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins10.1038/s41598-021-01809-y2045-2322https://doaj.org/article/5fd2824740524c3bbbaccdbeb52a3e102021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01809-yhttps://doaj.org/toc/2045-2322Abstract We recently found that nuclear receptor coactivator 7 (Ncoa7) and Oxr1 interact with the proton-pumping V-ATPase. Ncoa7 and Oxr1 belong to a group of proteins playing a role in the oxidative stress response, that contain the conserved “TLDc” domain. Here we asked if the three other proteins in this family, i.e., Tbc1d24, Tldc1 and Tldc2 also interact with the V-ATPase and if the TLDc domains are involved in all these interactions. By co-immunoprecipitation, endogenous kidney Tbc1d24 (and Ncoa7 and Oxr1) and overexpressed Tldc1 and Tldc2, all interacted with the V-ATPase. In addition, purified TLDc domains of Ncoa7, Oxr1 and Tldc2 (but not Tbc1d24 or Tldc1) interacted with V-ATPase in GST pull-downs. At the amino acid level, point mutations G815A, G845A and G896A in conserved regions of the Ncoa7 TLDc domain abolished interaction with the V-ATPase, and S817A, L926A and E938A mutations resulted in decreased interaction. Furthermore, poly-E motifs upstream of the TLDc domain in Ncoa7 and Tldc2 show a (nonsignificant) trend towards enhancing the interaction with V-ATPase. Our principal finding is that all five members of the TLDc family of proteins interact with the V-ATPase. We conclude that the TLDc motif defines a new class of V-ATPase interacting regulatory proteins.A. F. EatonD. BrownM. MerkulovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. F. Eaton D. Brown M. Merkulova The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins
description	Abstract We recently found that nuclear receptor coactivator 7 (Ncoa7) and Oxr1 interact with the proton-pumping V-ATPase. Ncoa7 and Oxr1 belong to a group of proteins playing a role in the oxidative stress response, that contain the conserved “TLDc” domain. Here we asked if the three other proteins in this family, i.e., Tbc1d24, Tldc1 and Tldc2 also interact with the V-ATPase and if the TLDc domains are involved in all these interactions. By co-immunoprecipitation, endogenous kidney Tbc1d24 (and Ncoa7 and Oxr1) and overexpressed Tldc1 and Tldc2, all interacted with the V-ATPase. In addition, purified TLDc domains of Ncoa7, Oxr1 and Tldc2 (but not Tbc1d24 or Tldc1) interacted with V-ATPase in GST pull-downs. At the amino acid level, point mutations G815A, G845A and G896A in conserved regions of the Ncoa7 TLDc domain abolished interaction with the V-ATPase, and S817A, L926A and E938A mutations resulted in decreased interaction. Furthermore, poly-E motifs upstream of the TLDc domain in Ncoa7 and Tldc2 show a (nonsignificant) trend towards enhancing the interaction with V-ATPase. Our principal finding is that all five members of the TLDc family of proteins interact with the V-ATPase. We conclude that the TLDc motif defines a new class of V-ATPase interacting regulatory proteins.
format	article
author	A. F. Eaton D. Brown M. Merkulova
author_facet	A. F. Eaton D. Brown M. Merkulova
author_sort	A. F. Eaton
title	The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins
title_short	The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins
title_full	The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins
title_fullStr	The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins
title_full_unstemmed	The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins
title_sort	evolutionary conserved tldc domain defines a new class of (h+)v-atpase interacting proteins
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5fd2824740524c3bbbaccdbeb52a3e10
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The evolutionary conserved TLDc domain defines a new class of (H+)V-ATPase interacting proteins

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