Structure and assembly of calcium homeostasis modulator proteins

Syrjanen, J. L., Michalski, K., Chou, T. H., Grant, T., Rao, S., Simorowski, N., Tucker, S. J., Grigorieff, N., Furukawa, H. (January 2020) Structure and assembly of calcium homeostasis modulator proteins. Nat Struct Mol Biol, 27 (2). pp. 150-159. ISSN 1545-9985 (Public Dataset)

DOI: 10.1038/s41594-019-0369-9


The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), through which ions and ATP permeate in a voltage-dependent manner to control neuronal excitability, taste signaling and pathologies of depression and Alzheimer's disease. Despite such critical biological roles, the structures and patterns of their oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single-particle cryo-electron microscopy (cryo-EM), which show novel assembly of the four transmembrane helices into channels of octamers and undecamers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore size, lipid accommodation and channel activity.

Item Type: Paper
Additional Information: Publisher Correction:
Subjects: Investigative techniques and equipment > microscopy > Cryo-electron microscopy
organs, tissues, organelles, cell types and functions > tissues types and functions > transport > membrane transport
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein structure rendering
CSHL Authors:
Communities: CSHL labs > Furukawa lab
Depositing User: Adrian Gomez
Date: 27 January 2020
Date Deposited: 10 Feb 2020 14:30
Last Modified: 22 Apr 2020 18:26
PMCID: PMC7015811
Related URLs:
Dataset ID:
  • Cryo-EM maps and structural coordinates generated during this study have been deposited in the Electron Microscopy Data Bank and Protein Data Bank with accession codes:
  • EMD-21143 and PDB 6VAM (chCALHM1), EMD-21141 and PDB 6VAK (hCALHM2), EMD-21140 and PDB 6VAI (hCALHM2 gap junction) and EMD-21142 and PDB 6VAL (chCALHM1–hCALHM2 chimera).

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