Structural highlights
Disease
[EMC1_HUMAN] Global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
[EMC10_HUMAN] Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways.[1] [MMGT1_HUMAN] Mediates Mg(2+) transport.[UniProtKB:Q8K273]
Publication Abstract from PubMed
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 ER membrane protein complex (EMC) is a conserved co- and post-translational insertase at the endoplasmic reticulum. We determined the structure of the human EMC in a lipid nanodisc to an overall resolution of 3.4 A 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.
Structural basis for membrane insertion by the human ER membrane protein complex.,Pleiner T, Pinton Tomaleri G, Januszyk K, Inglis AJ, Hazu M, Voorhees RM Science. 2020 May 21. pii: science.abb5008. doi: 10.1126/science.abb5008. PMID:32439656[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Reboll MR, Korf-Klingebiel M, Klede S, Polten F, Brinkmann E, Reimann I, Schonfeld HJ, Bobadilla M, Faix J, Kensah G, Gruh I, Klintschar M, Gaestel M, Niessen HW, Pich A, Bauersachs J, Gogos JA, Wang Y, Wollert KC. EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow-Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction. Circulation. 2017 Nov 7;136(19):1809-1823. doi:, 10.1161/CIRCULATIONAHA.117.029980. Epub 2017 Sep 20. PMID:28931551 doi:http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029980
- ↑ Pleiner T, Pinton Tomaleri G, Januszyk K, Inglis AJ, Hazu M, Voorhees RM. Structural basis for membrane insertion by the human ER membrane protein complex. Science. 2020 May 21. pii: science.abb5008. doi: 10.1126/science.abb5008. PMID:32439656 doi:http://dx.doi.org/10.1126/science.abb5008
