6WW7

Structure of the human ER membrane protein complex in a lipid nanodisc

Summary for 6WW7

• Entry DOI: 10.2210/pdb6ww7/pdb
• EMDB information: 21929 21930 21931
• Descriptor: ER membrane protein complex subunit 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: insertase, endoplasmic reticulum, transmembrane chaperone, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 9
• Total formula weight: 283671.79

Authors

Tomaleri, G.P.,Januszyk, K.,Pleiner, T.,Inglis, A.J.,Voorhees, R.M. (deposition date: 2020-05-08, release date: 2020-05-27, Last modification date: 2024-11-06)

Primary citation

Pleiner, T.,Tomaleri, G.P.,Januszyk, K.,Inglis, A.J.,Hazu, M.,Voorhees, R.M.
Structural basis for membrane insertion by the human ER membrane protein complex.
Science, 369:433-436, 2020

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 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.

PubMed: 32439656
DOI: 10.1126/science.abb5008

Experimental method

ELECTRON MICROSCOPY (3.4 Å)