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Cryo‐electron microscopy structure of CLHM1 ion channel from Caenorhabditis elegans
Author(s) -
Yang Weixin,
Wang Youwang,
Guo Jianli,
He Lingli,
Zhou Ye,
Zheng Hui,
Liu Zhenfeng,
Zhu Ping,
Zhang Xuejun C.
Publication year - 2020
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3904
Subject(s) - cryo electron microscopy , caenorhabditis elegans , ion channel , biophysics , chemistry , structural biology , cytoplasm , transmembrane protein , protein structure , crystallography , biochemistry , biology , receptor , gene
Calcium homeostasis modulators (CALHMs/CLHMs) comprise a family of pore‐forming protein complexes assembling into voltage‐gated, Ca 2+ ‐sensitive, nonselective channels. These complexes contain an ion‐conduction pore sufficiently wide to permit the passing of ATP molecules serving as neurotransmitters. While their function and structure information is accumulating, the precise mechanisms of these channel complexes remain to be full understood. Here, we present the structure of the Caenorhabditis elegans CLHM1 channel in its open state solved through single‐particle cryo‐electron microscopy at 3.7‐Å resolution. The transmembrane region of the channel structure of the dominant class shows an assembly of 10‐fold rotational symmetry in one layer, and its cytoplasmic region is involved in additional twofold symmetrical packing in a tail‐to‐tail manner. Furthermore, we identified a series of amino acid residues critical for the regulation of Ce CLHM1 channel using functional assays, electrophysiological analyses as well as structural‐based analysis. Our structure and function analyses provide new insights into the mechanisms of CALHM channels.