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Pore architecture of the ORAI1 store-operated calcium channel.

Authors
  • Zhou, Yubin1
  • Ramachandran, Sweta
  • Oh-Hora, Masatsugu
  • Rao, Anjana
  • Hogan, Patrick G
  • 1 Immune Disease Institute and Program in Cellular and Molecular Medicine, Children's Hospital Boston, 200 Longwood Avenue, Boston, MA 02115, USA.
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Mar 16, 2010
Volume
107
Issue
11
Pages
4896–4901
Identifiers
DOI: 10.1073/pnas.1001169107
PMID: 20194792
Source
Medline
License
Unknown

Abstract

ORAI1 is the pore-forming subunit of the calcium release-activated calcium (CRAC) channel, a store-operated channel that is central to Ca(2+) 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 Ca(2+). 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 Ca(2+) 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.

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