Cryo-EM structures and functional properties of CALHM channels of the human placenta.

Drożdżyk, Katarzyna; Sawicka, Marta; Bahamonde-Santos, Maria-Isabel; Zaugg, Jonas; Deneka, Dawid; Albrecht, Christiane; Dutzler, Raimund (2020). Cryo-EM structures and functional properties of CALHM channels of the human placenta. eLife, 9 eLife Sciences Publications 10.7554/eLife.55853

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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 found 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Zaugg, Jonas and Albrecht, Christiane

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2050-084X

Publisher:

eLife Sciences Publications

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

28 May 2020 17:55

Last Modified:

28 May 2020 21:17

Publisher DOI:

10.7554/eLife.55853

PubMed ID:

32374262

Uncontrolled Keywords:

human molecular biophysics structural biology

BORIS DOI:

10.7892/boris.144150

URI:

https://boris.unibe.ch/id/eprint/144150

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