+Search query
-Structure paper
Title | Structural basis for membrane insertion by the human ER membrane protein complex. |
---|---|
Journal, issue, pages | Science, Vol. 369, Issue 6502, Page 433-436, Year 2020 |
Publish date | Jul 24, 2020 |
Authors | Tino Pleiner / Giovani Pinton Tomaleri / Kurt Januszyk / Alison J Inglis / Masami Hazu / Rebecca M Voorhees / |
PubMed 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 ...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 links | Science / PubMed:32439656 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.2 - 3.6 Å |
Structure data | EMDB-21929: Human ER membrane protein complex in a lipid nanodisc, overall map EMDB-21930: Human ER membrane protein complex in a lipid nanodisc, multi-body refinement, lumenal map EMDB-21931: Human ER membrane protein complex in a lipid nanodisc, multi-body refinement, cytosolic map |
Chemicals | ChemComp-NAG: |
Source |
|
Keywords | MEMBRANE PROTEIN / Insertase / endoplasmic reticulum / transmembrane chaperone |