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Structural basis for membrane insertion by the human ER membrane protein complex.

ABSTRACT: A defining step in the biogenesis of a membrane protein is the insertion of its hydrophobic transmembrane helices into the lipid bilayer. The nine-subunit endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved co- and posttranslational insertase at the ER. We determined the structure of the human EMC in a lipid nanodisc to an overall resolution of 3.4 angstroms by cryo-electron microscopy, permitting building of a nearly complete atomic model. We used structure-guided mutagenesis to demonstrate that substrate insertion requires a methionine-rich cytosolic loop and occurs via an enclosed hydrophilic vestibule within the membrane formed by the subunits EMC3 and EMC6. We propose that the EMC uses local membrane thinning and a positively charged patch to decrease the energetic barrier for insertion into the bilayer.

SUBMITTER: Pleiner T

PROVIDER: S-EPMC7547852 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Structural basis for membrane insertion by the human ER membrane protein complex.

Pleiner Tino T Tomaleri Giovani Pinton GP Januszyk Kurt K Inglis Alison J AJ Hazu Masami M Voorhees Rebecca M RM

Science (New York, N.Y.) 20200521 6502

A defining step in the biogenesis of a membrane protein is the insertion of its hydrophobic transmembrane helices into the lipid bilayer. The nine-subunit endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved co- and posttranslational insertase at the ER. We determined the structure of the human EMC in a lipid nanodisc to an overall resolution of 3.4 angstroms by cryo-electron microscopy, permitting building of a nearly complete atomic model. We used structure-guided mutagenes ...[more]

PMID: 32439656

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