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

<div class='caption-title'>Expression analysis of CALHM genes in the human placenta.</div>
<div class='caption-title'>Comparative mRNA expression data for other physiologically relevant transporters/receptors in the human placenta.</div>
<div class='caption-title'>Functional characterization of CALHM channels expressed in X. laevis oocytes.</div>
Drożdżyk K, Sawicka M, Bahamonde-Santos MI, Jonas Z, Deneka D, Albrecht C, Dutzler R
OpenAccess logo Elife 9 (2020)
Related entries: 6ytk, 6ytl, 6yto, 6ytq, 6ytv

Cited: 14 times
EuropePMC logo PMID: 32374262

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.

Reviews - 6ytx mentioned but not cited (1)

  1. On the molecular nature of large-pore channels. Syrjanen J, Michalski K, Kawate T, Furukawa H. J Mol Biol 433 166994 (2021)

Articles - 6ytx mentioned but not cited (1)

  1. Cryo-EM structures and functional properties of CALHM channels of the human placenta. Drożdżyk K, Sawicka M, Bahamonde-Santos MI, Jonas Z, Deneka D, Albrecht C, Dutzler R. Elife 9 e55853 (2020)


Reviews citing this publication (2)

  1. Taste transduction and channel synapses in taste buds. Taruno A, Nomura K, Kusakizako T, Ma Z, Nureki O, Foskett JK. Pflugers Arch 473 3-13 (2021)
  2. To Be or Not to Be an Ion Channel: Cryo-EM Structures Have a Say. Chen GL, Li J, Zhang J, Zeng B. Cells 12 1870 (2023)

Articles citing this publication (10)

  1. Letter Cryo-EM structures of human calcium homeostasis modulator 5. Liu J, Wan F, Jin Q, Li X, Bhat EA, Guo J, Lei M, Guan F, Wu J, Ye S. Cell Discov 6 81 (2020)
  2. Structure versus function: Are new conformations of pannexin 1 yet to be resolved? Mim C, Perkins G, Dahl G. J Gen Physiol 153 e202012754 (2021)
  3. Cryo-EM structure of the heptameric calcium homeostasis modulator 1 channel. Ren Y, Li Y, Wang Y, Wen T, Lu X, Chang S, Zhang X, Shen Y, Yang X. J Biol Chem 298 101838 (2022)
  4. Cryo-EM structures of an LRRC8 chimera with native functional properties reveal heptameric assembly. Takahashi H, Yamada T, Denton JS, Strange K, Karakas E. Elife 12 e82431 (2023)
  5. The ion channel CALHM6 controls bacterial infection-induced cellular cross-talk at the immunological synapse. Danielli S, Ma Z, Pantazi E, Kumar A, Demarco B, Fischer FA, Paudel U, Weissenrieder J, Lee RJ, Joyce S, Foskett JK, Bezbradica JS. EMBO J 42 e111450 (2023)
  6. Cryo-electron microscopy structure of CLHM1 ion channel from Caenorhabditis elegans. Yang W, Wang Y, Guo J, He L, Zhou Y, Zheng H, Liu Z, Zhu P, Zhang XC. Protein Sci 29 1803-1815 (2020)
  7. Intramolecular Disulfide Bonds for Biogenesis of CALHM1 Ion Channel Are Dispensable for Voltage-Dependent Activation Kwon JW, Jeon YK, Kim J, Kim SJ, Kim SJ. Mol Cells 44 758-769 (2021)
  8. Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels. Kern DM, Bleier J, Mukherjee S, Hill JM, Kossiakoff AA, Isacoff EY, Brohawn SG. Nat Struct Mol Biol (2023)
  9. Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red. Syrjänen JL, Epstein M, Gómez R, Furukawa H. Nat Commun 14 3821 (2023)
  10. When is a hydrophobic gate not a hydrophobic gate? Seiferth D, Biggin PC, Tucker SJ. J Gen Physiol 154 e202213210 (2022)


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