2K60: NMR structure of calcium-loaded STIM1 EF-SAM

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.
PDB ID: 2K60Download
MMDB ID: 67121
PDB Deposition Date: 2008/7/2
Updated in MMDB: 2008/10
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2K60: monomeric; determined by author
Molecular Components in 2K60
Label Count Molecule
Protein (1 molecule)
Protein (Stromal Interaction Molecule 1)(Gene symbol: STIM1)
Molecule annotation
Chemicals (2 molecules)
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