Defects in the STIM1 SOARα2 domain affect multiple steps in the CRAC channel activation cascade.

ABSTRACT: The calcium release-activated calcium (CRAC) channel consists of STIM1, a Ca²⁺ sensor in the endoplasmic reticulum (ER), and Orai1, the Ca²⁺ ion channel in the plasma membrane. Ca²⁺ store depletion triggers conformational changes and oligomerization of STIM1 proteins and their direct interaction with Orai1. Structural alterations include the transition of STIM1 C-terminus from a folded to an extended conformation thereby exposing CAD (CRAC activation domain)/SOAR (STIM1-Orai1 activation region) for coupling to Orai1. In this study, we discovered that different point mutations of F394 in the small alpha helical segment (STIM1 α2) within the CAD/SOAR apex entail a rich plethora of effects on diverse STIM1 activation steps. An alanine substitution (STIM1 F394A

SUBMITTER: Hoglinger C 

PROVIDER: S-EPMC8558294 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature