Cryo-EM structures and functional properties of CALHM channels of the human placenta
| Autor: | Zaugg Jonas, Katarzyna Drożdżyk, Raimund Dutzler, Marta Sawicka, Christiane Albrecht, Dawid Deneka, Maria-Isabel Bahamonde-Santos |
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| Přispěvatelé: | University of Zurich, Dutzler, Raimund |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Conformational change Cryo-electron microscopy Protein Conformation Structural Biology and Molecular Biophysics Membrane Potentials 0302 clinical medicine Pregnancy 2400 General Immunology and Microbiology Conus Biology (General) 610 Medicine & health CALHM channels 0303 health sciences Membrane Glycoproteins biology Chemistry General Neuroscience 2800 General Neuroscience General Medicine medicine.anatomical_structure Medicine Female Intracellular Research Article Human placenta QH301-705.5 Science transcription analysis cryo-electron microscopy General Biochemistry Genetics and Molecular Biology lipids 03 medical and health sciences Membrane Lipids Structure-Activity Relationship 1300 General Biochemistry Genetics and Molecular Biology Placenta medicine 10019 Department of Biochemistry Humans 030304 developmental biology General Immunology and Microbiology Cryoelectron Microscopy Trophoblast biology.organism_classification electrophysiology Electrophysiology HEK293 Cells Structural biology Biophysics 570 Life sciences CALHM1 Calcium Channels 030217 neurology & neurosurgery |
| Zdroj: | eLife eLife, Vol 9 (2020) 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 |
| DOI: | 10.7554/eLife.55853 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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