High affinity associations with α-SNAP enable calcium entry via Orai1 channels.

Molecular steps that activate store-operated calcium entry (SOCE) via Orai channel supramolecular complex remain incompletely defined. We have earlier shown that α-SNAP regulates the on-site functional assembly and calcium selectivity of Orai1 channels. Here we investigate the molecular basis of its...

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Autores principales:	Ramanagouda Ramanagoudr-Bhojappa, Yong Miao, Monika Vig
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ea790ac24fe427a884293ec325154a3
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spelling	oai:doaj.org-article:9ea790ac24fe427a884293ec325154a32021-12-02T20:16:52ZHigh affinity associations with α-SNAP enable calcium entry via Orai1 channels.1932-620310.1371/journal.pone.0258670https://doaj.org/article/9ea790ac24fe427a884293ec325154a32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258670https://doaj.org/toc/1932-6203Molecular steps that activate store-operated calcium entry (SOCE) via Orai channel supramolecular complex remain incompletely defined. We have earlier shown that α-SNAP regulates the on-site functional assembly and calcium selectivity of Orai1 channels. Here we investigate the molecular basis of its association with Orai, Stim and find that the affinity of α-SNAP for Orai and Stim is substantially higher than previously reported affinities between Stim and Orai sub-domains. α-SNAP binds the coiled-coil 3 (CC3) sub-domain of Stim1. Mutations of Tryptophan 430 in Stim1-CC3 disrupted α-SNAP association and SOCE, demonstrating a novel α-SNAP dependent function for this crucial subdomain. Further, α-SNAP binds the hinge region near the C-terminus of Orai1 and an additional broad region near the N-terminus and Valine 262 and Leucine 74 were necessary for these respective interactions, but not Orai, Stim co-clustering. Thus, high affinity interactions with α-SNAP are necessary for imparting functionality to Stim, Orai clusters and induction of SOCE.Ramanagouda Ramanagoudr-BhojappaYong MiaoMonika VigPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258670 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ramanagouda Ramanagoudr-Bhojappa Yong Miao Monika Vig High affinity associations with α-SNAP enable calcium entry via Orai1 channels.
description	Molecular steps that activate store-operated calcium entry (SOCE) via Orai channel supramolecular complex remain incompletely defined. We have earlier shown that α-SNAP regulates the on-site functional assembly and calcium selectivity of Orai1 channels. Here we investigate the molecular basis of its association with Orai, Stim and find that the affinity of α-SNAP for Orai and Stim is substantially higher than previously reported affinities between Stim and Orai sub-domains. α-SNAP binds the coiled-coil 3 (CC3) sub-domain of Stim1. Mutations of Tryptophan 430 in Stim1-CC3 disrupted α-SNAP association and SOCE, demonstrating a novel α-SNAP dependent function for this crucial subdomain. Further, α-SNAP binds the hinge region near the C-terminus of Orai1 and an additional broad region near the N-terminus and Valine 262 and Leucine 74 were necessary for these respective interactions, but not Orai, Stim co-clustering. Thus, high affinity interactions with α-SNAP are necessary for imparting functionality to Stim, Orai clusters and induction of SOCE.
format	article
author	Ramanagouda Ramanagoudr-Bhojappa Yong Miao Monika Vig
author_facet	Ramanagouda Ramanagoudr-Bhojappa Yong Miao Monika Vig
author_sort	Ramanagouda Ramanagoudr-Bhojappa
title	High affinity associations with α-SNAP enable calcium entry via Orai1 channels.
title_short	High affinity associations with α-SNAP enable calcium entry via Orai1 channels.
title_full	High affinity associations with α-SNAP enable calcium entry via Orai1 channels.
title_fullStr	High affinity associations with α-SNAP enable calcium entry via Orai1 channels.
title_full_unstemmed	High affinity associations with α-SNAP enable calcium entry via Orai1 channels.
title_sort	high affinity associations with α-snap enable calcium entry via orai1 channels.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9ea790ac24fe427a884293ec325154a3
work_keys_str_mv	AT ramanagoudaramanagoudrbhojappa highaffinityassociationswithasnapenablecalciumentryviaorai1channels AT yongmiao highaffinityassociationswithasnapenablecalciumentryviaorai1channels AT monikavig highaffinityassociationswithasnapenablecalciumentryviaorai1channels
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High affinity associations with α-SNAP enable calcium entry via Orai1 channels.

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