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TitleCryo-EM structures and functional properties of CALHM channels of the human placenta.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateMay 6, 2020
AuthorsKatarzyna Drożdżyk / Marta Sawicka / Maria-Isabel Bahamonde-Santos / Zaugg Jonas / Dawid Deneka / Christiane Albrecht / Raimund Dutzler /
PubMed AbstractThe 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 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.
External linksElife / PubMed:32374262 / PubMed Central
MethodsEM (single particle)
Resolution3.82 - 6.23 Å
Structure data

10917

6ytk

EMDB-10917, PDB-6ytk:
Cryo-EM structure of a dimer of decameric human CALHM4 in the absence of Ca2+
Method: EM (single particle) / Resolution: 4.07 Å

10919

6ytl

EMDB-10919, PDB-6ytl:
Cryo-EM structure of a dimer of undecameric human CALHM4 in the absence of Ca2+
Method: EM (single particle) / Resolution: 3.82 Å

10920

6yto

EMDB-10920, PDB-6yto:
Cryo-EM structure of a dimer of decameric human CALHM4 in the presence of Ca2+
Method: EM (single particle) / Resolution: 4.24 Å

10921

6ytq

EMDB-10921, PDB-6ytq:
Cryo-EM structure of a dimer of undecameric human CALHM4 in the presence of Ca2+
Method: EM (single particle) / Resolution: 4.02 Å

10924

6ytv

EMDB-10924, PDB-6ytv:
Cryo-EM structure of decameric human CALHM6 in the presence of Ca2+
Method: EM (single particle) / Resolution: 4.39 Å

10925

6ytx

EMDB-10925, PDB-6ytx:
Cryo-EM structure of undecameric human CALHM6 in the presence of Ca2+
Method: EM (single particle) / Resolution: 6.23 Å

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / calcium homeostasis modulator / ion channel / placenta

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