Cryo-EM structure of type 1 IP3R channel in a lipid bilayer

Mariah R. Baker, Guizhen Fan, Alexander B. Seryshev, Melina A. Agosto, Matthew L. Baker, Irina I. Serysheva

Résultat de recherche: Articleexamen par les pairs

22 Citations (Scopus)

Résumé

Type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) is the predominant Ca2+-release channel in neurons. IP3R1 mediates Ca2+ release from the endoplasmic reticulum into the cytosol and thereby is involved in many physiological processes. Here, we present the cryo-EM structures of full-length rat IP3R1 reconstituted in lipid nanodisc and detergent solubilized in the presence of phosphatidylcholine determined in ligand-free, closed states by single-particle electron cryo-microscopy. Notably, both structures exhibit the well-established IP3R1 protein fold and reveal a nearly complete representation of lipids with similar locations of ordered lipids bound to the transmembrane domains. The lipid-bound structures show improved features that enabled us to unambiguously build atomic models of IP3R1 including two membrane associated helices that were not previously resolved in the TM region. Our findings suggest conserved locations of protein-bound lipids among homotetrameric ion channels that are critical for their structural and functional integrity despite the diversity of structural mechanisms for their gating.

Langue d'origineEnglish
Numéro d'article625
JournalCommunications Biology
Volume4
Numéro de publication1
DOI
Statut de publicationPublished - déc. 2021
Publié à l'externeOui

Note bibliographique

Funding Information:
This work was supported by grants from the National Institutes of Health (R01GM072804, R21NS106968, R01EY026545, R01EY025218, P01GM063210), American Heart Association (18CDA34110086), and Welch Foundation (AU-2014-20190330).

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus Subject Areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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