期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 15, 页码 5657-5662出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1118947109
关键词
crystal structure; SOAR; store-operated calcium entry; Stromal interaction molecule
资金
- 973 Program [2009CB825504, 2012CB917201]
- National Nature Science Foundation of China [31170684]
- Tianjin Basic Research program [08QTPTJC28200, 08SYSYTC00200]
- Fundamental Research Funds for the Central Universities [65020241]
Calcium influx through the Ca2+ release-activated Ca2+ (CRAC) channel is an essential process in many types of cells. Upon store depletion, the calcium sensor in the endoplasmic reticulum, STIM1, activates Orai1, a CRAC channel in the plasma membrane. We have determined the structures of SOAR from Homo sapiens (hSOAR), which is part of STIM1 and is capable of constitutively activating Orai1, and the entire coiled coil region of STIM1 from Caenorhabditis elegans (ceSTIM1-CCR) in an inactive state. Our studies reveal that the formation of a SOAR dimer is necessary to activate the Orai1 channel. Mutations that disrupt SOAR dimerization or remove the cluster of positive residues abolish STIM1 activation of Orai1. We identified a possible inhibitory helix within the structure of ceSTIM1-CCR that tightly interacts with SOAR. Functional studies suggest that the inhibitory helix may keep the C-terminus of STIM1 in an inactive state. Our data allowed us to propose a model for STIM1 activation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据