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TitleStructural basis for membrane insertion by the human ER membrane protein complex.
Journal, issue, pagesScience, Vol. 369, Issue 6502, Page 433-436, Year 2020
Publish dateJul 24, 2020
AuthorsTino Pleiner / Giovani Pinton Tomaleri / Kurt Januszyk / Alison J Inglis / Masami Hazu / Rebecca M Voorhees /
PubMed AbstractA 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 ...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.
External linksScience / PubMed:32439656 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.6 Å
Structure data

21929

6ww7

EMDB-21929: Human ER membrane protein complex in a lipid nanodisc, overall map
PDB-6ww7: Structure of the human ER membrane protein complex in a lipid nanodisc
Method: EM (single particle) / Resolution: 3.4 Å

21930

6ww7

EMDB-21930: Human ER membrane protein complex in a lipid nanodisc, multi-body refinement, lumenal map
PDB-6ww7: Structure of the human ER membrane protein complex in a lipid nanodisc
Method: EM (single particle) / Resolution: 3.2 Å

21931

6ww7

EMDB-21931: Human ER membrane protein complex in a lipid nanodisc, multi-body refinement, cytosolic map
PDB-6ww7: Structure of the human ER membrane protein complex in a lipid nanodisc
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • Human (human)
KeywordsMEMBRANE PROTEIN / Insertase / endoplasmic reticulum / transmembrane chaperone

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