Pore architecture of the ORAI1 store-operated calcium channel

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

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4896-4901
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number11
DOIs
Publication statusPublished - Mar 16 2010
Externally publishedYes

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Calcium Channels
Cysteine
Disulfides
Binding Sites
Ions

All Science Journal Classification (ASJC) codes

  • General

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Pore architecture of the ORAI1 store-operated calcium channel. / Zhou, Yubin; Ramachandran, Sweta; Oh-hora, Masatsugu; Rao, Anjana; Hogan, Patrick G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 11, 16.03.2010, p. 4896-4901.

Research output: Contribution to journalArticle

Zhou, Yubin ; Ramachandran, Sweta ; Oh-hora, Masatsugu ; Rao, Anjana ; Hogan, Patrick G. / Pore architecture of the ORAI1 store-operated calcium channel. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 11. pp. 4896-4901.
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