6VTK

Structure of an acid-sensing ion channel solubilized by styrene maleic acid and in a desensitized state at low pH

Summary for 6VTK

• Entry DOI: 10.2210/pdb6vtk/pdb
• EMDB information: 21380
• Descriptor: Acid-sensing ion channel 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: ion channel, ligand-gated ion channel, acid-sensing ion channel, asic, asic1a, proton-gated ion channel, membrane protein, transport protein
• Biological source: Gallus gallus (Chicken)
• Total number of polymer chains: 3
• Total formula weight: 181568.22

Authors

Yoder, N.,Gouaux, E. (deposition date: 2020-02-12, release date: 2020-03-11, Last modification date: 2024-10-23)

Primary citation

Yoder, N.,Gouaux, E.
The His-Gly motif of acid-sensing ion channels resides in a reentrant 'loop' implicated in gating and ion selectivity.
Elife, 9:-, 2020

PubMed Abstract: Acid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout the central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here, we extract full-length chicken ASIC1 (cASIC1) from cell membranes using styrene maleic acid (SMA) copolymer, elucidating structures of ASIC1 channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1 that includes the highly conserved 'His-Gly' (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the 'Gly-Ala-Ser' (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.

PubMed: 32496192
DOI: 10.7554/eLife.56527

Experimental method

ELECTRON MICROSCOPY (2.82 Å)