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Sterol hindrance of Orai activation

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Science Signaling  08 Mar 2016:
Vol. 9, Issue 418, pp. fs4
DOI: 10.1126/scisignal.aaf2357


  • Fig. 1 Hypothetical model for cholesterol-Orai interactions.

    To illustrate the putative cholesterol-binding site, the Drosophila Orai structure [Protein Data Bank (PDB) accession number 4HKR] (7) was modified to match the sequence of human Orai1 by replacing Gln152 with Tyr. (A) (left) Human Orai1 is depicted in association with the STIM-Orai activating region (SOAR; PDB accession number 3TEQ) (11). (right) The N-terminal end of TM1 in human Orai1 was replaced with a 310 helix, a conformation that might favor association with cholesterol at the expense of SOAR. (B) Detailed view of hypothetical SOAR-Orai1 interaction in cholesterol-free Orai1. (C) Detailed view of hypothetical cholesterol-Orai1 interaction. (D) End-on view of Orai1-TM1 as an α-helix, to illustrate the orientation of Leu74 and Tyr80 side chains in this conformation. (E) End-on view of Orai1-TM1 as a 310-helix to illustrate the orientation of the key cholesterol-binding residues in this conformation.

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