2MAJ

Solution Structure of the STIM1 CC1-CC2 homodimer.

2MAJ の概要

• エントリーDOI: 10.2210/pdb2maj/pdb
• 関連するPDBエントリー: 2MAK
• NMR情報: BMRB: 19362
• 分子名称: Stromal interaction molecule 1 (1 entity in total)
• 機能のキーワード: stim1, coiled-coil, transport protein, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: Q13586
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19405.98

構造登録者

Stathopulos, P.B.,Ikura, M. (登録日: 2013-07-12, 公開日: 2014-01-15, 最終更新日: 2024-05-01)

主引用文献

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

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: 24351972
DOI: 10.1038/ncomms3963

実験手法

SOLUTION NMR