Pore architecture of the ORAI1 store-operated calcium channel

Yubin Zhou, Sweta Ramachandran, Masatsugu Oh-hora, Anjana Rao, Patrick G. Hogan

研究成果: ジャーナルへの寄稿学術誌査読

126 被引用数 (Scopus)


ORAI1 is the pore-forming subunit of the calcium release-activated calcium (CRAC) channel, a store-operated channel that is central to Ca2b2+ signaling in mammalian cells. Electrophysiological data have shown that the acidic residues E106 in transmembrane helix 1 (TM1) and E190 in TM3 contribute to the high selectivity of ORAI1 channels for Ca2b2+. We have examined the pore architecture of the ORAI1 channel using ORAI1 proteins engineered to contain either one or two cysteine residues. Disulfide cross-linking shows that ORAI1 assembles as a tetramer or a higher oligomer with TM1 centrally located. Cysteine side chains projecting from TM1 at position 88, 95, 102, or 106 cross-link efficiently to the corresponding side chain in a second ORAI1 monomer. Cysteine residues at position 190 or at surrounding positions in TM3 do not cross-link. We conclude that E106 residues in wild-type ORAI1 are positioned to form a Ca2b2+ binding site in the channel pore and that E190 interacts less directly with ions traversing the pore. The cross-linking data further identify a relatively rigid segment of TM1 adjacent to E106 that is likely to contribute to the selectivity filter.

ジャーナルProceedings of the National Academy of Sciences of the United States of America
出版ステータス出版済み - 3月 16 2010

!!!All Science Journal Classification (ASJC) codes

  • 一般


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