6YTO

Cryo-EM structure of a dimer of decameric human CALHM4 in the presence of Ca2+

Summary for 6YTO

• Entry DOI: 10.2210/pdb6yto/pdb
• EMDB information: 10917 10919 10920
• Descriptor: Calcium homeostasis modulator protein 4 (1 entity in total)
• Functional Keywords: calcium homeostasis modulator, ion channel, placenta, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 20
• Total formula weight: 701872.82

Authors

Sawicka, M.,Drozdzyk, K.,Dutzler, R. (deposition date: 2020-04-24, release date: 2020-05-13, Last modification date: 2024-10-16)

Primary citation

Drozdzyk, K.,Sawicka, M.,Bahamonde-Santos, M.I.,Jonas, Z.,Deneka, D.,Albrecht, C.,Dutzler, R.
Cryo-EM structures and functional properties of CALHM channels of the human placenta.
Elife, 9:-, 2020

PubMed Abstract: The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in the human placenta. By transcript analysis, we found the paralogs CALHM2, 4, and 6 to be highly expressed in this organ and upregulated during trophoblast differentiation. Based on electrophysiology, we observed that activation of these paralogs differs from the voltage- and calcium-gated channel CALHM1. Cryo-EM structures of CALHM4 display decameric and undecameric assemblies with large cylindrical pore, while in CALHM6 a conformational change has converted the pore shape into a conus that narrows at the intracellular side, thus describing distinct functional states of the channel. The pore geometry alters the distribution of lipids, which occupy the cylindrical pore of CALHM4 in a bilayer-like arrangement whereas they have redistributed in the conical pore of CALHM6 with potential functional consequences.

PubMed: 32374262
DOI: 10.7554/eLife.55853

Experimental method

ELECTRON MICROSCOPY (4.24 Å)