Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.

Abstract:

:The calcium release-activated calcium channel Orai regulates Ca2+ entry into non-excitable cells and is required for proper immune function. While the channel typically opens following Ca2+ release from the endoplasmic reticulum, certain pathologic mutations render the channel constitutively open. Previously, using one such mutation (H206A), we obtained low (6.7 Å) resolution X-ray structural information on Drosophila melanogaster Orai in an open conformation (Hou et al., 2018). Here we present a structure of this open conformation at 3.3 Å resolution using fiducial-assisted cryo-electron microscopy. The improved structure reveals the conformations of amino acids in the open pore, which dilates by outward movements of subunits. A ring of phenylalanine residues repositions to expose previously shielded glycine residues to the pore without significant rotational movement of the associated helices. Together with other hydrophobic amino acids, the phenylalanines act as the channel's gate. Structured M1-M2 turrets, not evident previously, form the channel's extracellular entrance.

journal_name

Elife

journal_title

eLife

authors

Hou X,Outhwaite IR,Pedi L,Long SB

doi

10.7554/eLife.62772

subject

Has Abstract

pub_date

2020-11-30 00:00:00

issn

2050-084X

pii

62772

journal_volume

9

pub_type

杂志文章

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