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TitleCryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies.
Journal, issue, pagesSci Adv, Vol. 6, Issue 29, Page eaba8105, Year 2020
Publish dateJul 17, 2020
AuthorsKanae Demura / Tsukasa Kusakizako / Wataru Shihoya / Masahiro Hiraizumi / Kengo Nomura / Hiroto Shimada / Keitaro Yamashita / Tomohiro Nishizawa / Akiyuki Taruno / Osamu Nureki /
PubMed AbstractCalcium homeostasis modulator (CALHM) family proteins are Ca-regulated adenosine triphosphate (ATP)-release channels involved in neural functions including neurotransmission in gustation. Here, we ...Calcium homeostasis modulator (CALHM) family proteins are Ca-regulated adenosine triphosphate (ATP)-release channels involved in neural functions including neurotransmission in gustation. Here, we present the cryo-electron microscopy (EM) structures of killifish CALHM1, human CALHM2, and CLHM-1 at resolutions of 2.66, 3.4, and 3.6 Å, respectively. The CALHM1 octamer structure reveals that the N-terminal helix forms the constriction site at the channel pore in the open state and modulates the ATP conductance. The CALHM2 undecamer and CLHM-1 nonamer structures show the different oligomeric stoichiometries among CALHM homologs. We further report the cryo-EM structures of the chimeric construct, revealing that the intersubunit interactions at the transmembrane domain (TMD) and the TMD-intracellular domain linker define the oligomeric stoichiometry. These findings advance our understanding of the ATP conduction and oligomerization mechanisms of CALHM channels.
External linksSci Adv / PubMed:32832629 / PubMed Central
MethodsEM (single particle)
Resolution2.66 - 3.6 Å
Structure data

0919

6lmt

EMDB-0919, PDB-6lmt:
Cryo-EM structure of the killifish CALHM1
Method: EM (single particle) / Resolution: 2.66 Å

0920

6lmu

EMDB-0920, PDB-6lmu:
Cryo-EM structure of the human CALHM2
Method: EM (single particle) / Resolution: 3.4 Å

0921

6lmv

EMDB-0921, PDB-6lmv:
Cryo-EM structure of the C. elegans CLHM-1
Method: EM (single particle) / Resolution: 3.6 Å

0922

6lmw

EMDB-0922, PDB-6lmw:
Cryo-EM structure of the CALHM chimeric construct (8-mer)
Method: EM (single particle) / Resolution: 3.4 Å

0923

6lmx

EMDB-0923, PDB-6lmx:
Cryo-EM structure of the CALHM chimeric construct (9-mer)
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

Source
  • oryzias latipes (Japanese medaka)
  • homo sapiens (human)
  • caenorhabditis elegans (invertebrata)
KeywordsMEMBRANE PROTEIN / channel

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