4o9b
From Proteopedia
The Structure of CC1-IH in human STIM1.
Structural highlights
DiseaseSTIM1_HUMAN Defects in STIM1 are the cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 2 (IDTICED2) [MIM:612783. IDTICED2 is an immune disorder characterized by recurrent infections, impaired T-cell activation and proliferative response, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, non-progressive myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.[1] FunctionSTIM1_HUMAN Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit, TMEM142A/ORAI1.[2] [3] [4] [5] [6] [7] [8] [9] [10] Publication Abstract from PubMedStore-operated Ca(2+) entry (SOCE) is a critical Ca(2+) signaling pathway in many cell types. After sensing Ca(2+) store depletion in the endoplasmic reticulum (ER) lumen, STIM1 (STromal Interaction Molecule 1) oligomerizes and then interacts with and activates the Orai1 calcium channel. Our previous research has demonstrated that the inhibitory helix (IH) adjacent to the first coiled-coil region (CC1) of STIM1 may keep the whole C-terminus of STIM1 in an inactive state. However, the specific conformational change of CC1-IH that drives the transition of STIM1 from the resting state to the active state remains elusive. Herein, we report the structural analysis of CC1-IH, which revealed that the entire CC1-IH molecule forms a very long helix. Structural and biochemical analyses indicated that IH, and not the CC1 region, contributes to the oligomerization of STIM1. Small-angle X-ray scattering (SAXS) analysis suggested that the C-terminus of STIM1 including the IH region displays a collapsed conformation, whereas the construct without the IH region has an extended conformation. These two conformations may correspond to the conformational states of the C-terminus of STIM1 before and after activation. Taken together, our results provide direct biochemical evidence that the IH region controls the conformational switching of the C-terminus of STIM1. The Inhibitory Helix Controls the Intramolecular Conformational Switching of the C-Terminus of STIM1.,Cui B, Yang X, Li S, Lin Z, Wang Z, Dong C, Shen Y PLoS One. 2013 Sep 19;8(9):e74735. doi: 10.1371/journal.pone.0074735. PMID:24069340[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Cui B | Li S | Shen Y | Yang X
