6VAK

Cryo-EM structure of human CALHM2

Summary for 6VAK

• Entry DOI: 10.2210/pdb6vak/pdb
• EMDB information: 21140 21141 21142 21143
• Descriptor: Calcium homeostasis modulator protein 2 (1 entity in total)
• Functional Keywords: assembly, taste, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 11
• Total formula weight: 412157.58

Authors

Syrjanen, J.L.,Chou, T.H.,Furukawa, H. (deposition date: 2019-12-17, release date: 2020-01-29, Last modification date: 2024-10-16)

Primary citation

Syrjanen, J.L.,Michalski, K.,Chou, T.H.,Grant, T.,Rao, S.,Simorowski, N.,Tucker, S.J.,Grigorieff, N.,Furukawa, H.
Structure and assembly of calcium homeostasis modulator proteins.
Nat.Struct.Mol.Biol., 27:150-159, 2020

PubMed Abstract: 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.

PubMed: 31988524
DOI: 10.1038/s41594-019-0369-9

Experimental method

ELECTRON MICROSCOPY (3.48 Å)