2MAK
Solution structure of the STIM1 CC1-CC2 homodimer in complex with two Orai1 C-terminal domains.
Summary for 2MAK
| Entry DOI | 10.2210/pdb2mak/pdb |
| Related | 2maj |
| NMR Information | BMRB: 19363 |
| Descriptor | Stromal interaction molecule 1, Calcium release-activated calcium channel protein 1 (2 entities in total) |
| Functional Keywords | stim1, orai1, coiled-coil, orai1 c-terminal domain, transport protein, signaling protein-transport protein complex, signaling protein/transport protein |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cell membrane; Single-pass type I membrane protein: Q13586 Cell membrane; Multi-pass membrane protein: Q96D31 |
| Total number of polymer chains | 4 |
| Total formula weight | 24715.59 |
| Authors | Stathopulos, P.B.,Ikura, M. (deposition date: 2013-07-12, release date: 2014-01-15, Last modification date: 2024-05-01) |
| Primary citation | Stathopulos, P.B.,Schindl, R.,Fahrner, M.,Zheng, L.,Gasmi-Seabrook, G.M.,Muik, M.,Romanin, C.,Ikura, M. STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry. Nat Commun, 4:2963-2963, 2013 Cited by PubMed Abstract: Orai1 calcium channels in the plasma membrane are activated by stromal interaction molecule-1 (STIM1), an endoplasmic reticulum calcium sensor, to mediate store-operated calcium entry (SOCE). The cytosolic region of STIM1 contains a long putative coiled-coil (CC)1 segment and shorter CC2 and CC3 domains. Here we present solution nuclear magnetic resonance structures of a trypsin-resistant CC1-CC2 fragment in the apo and Orai1-bound states. Each CC1-CC2 subunit forms a U-shaped structure that homodimerizes through antiparallel interactions between equivalent α-helices. The CC2:CC2' helix pair clamps two identical acidic Orai1 C-terminal helices at opposite ends of a hydrophobic/basic STIM-Orai association pocket. STIM1 mutants disrupting CC1:CC1' interactions attenuate, while variants promoting CC1 stability spontaneously activate Orai1 currents. CC2 mutations cause remarkable variability in Orai1 activation because of a dual function in binding Orai1 and autoinhibiting STIM1 oligomerization via interactions with CC3. We conclude that SOCE is activated through dynamic interplay between STIM1 and Orai1 helices. PubMed: 24351972DOI: 10.1038/ncomms3963 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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