Structure and assembly of calcium homeostasis modulator proteins [preprint]
Authors
Syrjanen, Johanna L.Michalski, Kevin
Chou, Tsung-Han
Grant, Timothy
Rao, Shanlin
Simorowski, Noriko
Tucker, Stephen J.
Grigorieff, Nikolaus
Furukawa, Hiro
UMass Chan Affiliations
RNA Therapeutics InstituteDocument Type
PreprintPublication Date
2019-11-27Keywords
calcium homeostasis modulator proteins (CALHMs)large-pore channels
lipids
Biophysics
Amino Acids, Peptides, and Proteins
Biophysics
Molecular Biology
Structural Biology
Metadata
Show full item recordAbstract
Biological membranes of many tissues and organs contain large-pore channels designed to permeate a wide variety of ions and metabolites. 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), which permeate ions and ATP 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 oligomeric assembly remain unclear. Here, we reveal the first structures of two CALHMs, CALHM1 and CALHM2, by single particle cryo-electron microscopy, which show novel assembly of the four transmembrane helices into channels of 8-mers and 11-mers, 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.Source
bioRxiv 857698; doi: https://doi.org/10.1101/857698. Link to preprint on bioRxiv service.
DOI
10.1101/857698Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29435Related Resources
Now published in Nature Structural & Molecular Biology doi: 10.1038/s41594-019-0369-9
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.Distribution License
http://creativecommons.org/licenses/by-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/857698
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.