2k60 | pdb_00002k60

NMR structure of calcium-loaded STIM1 EF-SAM

spinqualitylabelsall models 2k60, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2k60 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Gene: STIM1, GOK (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Disease [STIM1_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. Function [STIM1_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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Stromal interaction molecule-1 (STIM1) activates store-operated Ca2+ entry (SOCE) in response to diminished luminal Ca2+ levels. Here, we present the atomic structure of the Ca2+-sensing region of STIM1 consisting of the EF-hand and sterile alpha motif (SAM) domains (EF-SAM). The canonical EF-hand is paired with a previously unidentified EF-hand. Together, the EF-hand pair mediates mutually indispensable hydrophobic interactions between the EF-hand and SAM domains. Structurally critical mutations in the canonical EF-hand, "hidden" EF-hand, or SAM domain disrupt Ca2+ sensitivity in oligomerization via destabilization of the entire EF-SAM entity. In mammalian cells, EF-SAM destabilization mutations within full-length STIM1 induce punctae formation and activate SOCE independent of luminal Ca2+. We provide atomic resolution insight into the molecular basis for STIM1-mediated SOCE initiation and show that the folded/unfolded state of the Ca2+-sensing region of STIM is crucial to SOCE regulation. Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry.,Stathopulos PB, Zheng L, Li GY, Plevin MJ, Ikura M Cell. 2008 Oct 3;135(1):110-22. PMID:18854159 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA