Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.6 (
CAD
)
4,420
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
STIM1 and
STIM2
are endoplasmic reticulum (ER) membrane proteins that sense decreases in ER-luminal free Ca
2+
and, through a conformational change in the STIM cytoplasmic domain, control gating of the plasma membrane Ca
2+
channel ORAI1. To determine how STIM1 conveys a signal from the ER lumen to the cytoplasm, we studied the Ca
2+
-dependent conformational change of engineered STIM1 proteins in isolated ER membranes and, in parallel, physiological activation of these proteins in cells. We find that conserved "sentinel" features of the CC1 region help to prevent activation while Ca
2+
is bound to STIM ER-luminal domains. Reduced ER-luminal Ca
2+
drives a concerted conformational change, in which STIM luminal domains rearrange and the STIM transmembrane helices and initial parts of the CC1 regions pair in an extended coiled coil. This intradimer rearrangement overcomes the relatively weak CC1-SOAR/
CAD
interactions that hold STIM in an inactive conformation, releasing the SOAR/
CAD
domain to activate ORAI channels.
...
PMID:Coiled-Coil Formation Conveys a STIM1 Signal from ER Lumen to Cytoplasm. 2929 34
