Identification of Oxa1 Homologs Operating in the Eukaryotic Endoplasmic Reticulum.

S Andrei Anghel, Philip T McGilvray, Ramanujan S Hegde, Robert J Keenan

Cell reports 2017 Dec 26

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Members of the evolutionarily conserved Oxa1/Alb3/YidC family mediate membrane protein biogenesis at the mitochondrial inner membrane, chloroplast thylakoid membrane, and bacterial plasma membrane, respectively. Despite their broad phylogenetic distribution, no Oxa1/Alb3/YidC homologs are known to operate in eukaryotic cells outside the endosymbiotic organelles. Here, we present bioinformatic evidence that the tail-anchored protein insertion factor WRB/Get1, the "endoplasmic reticulum (ER) membrane complex" subunit EMC3, and TMCO1 are ER-resident homologs of the Oxa1/Alb3/YidC family. Topology mapping and co-evolution-based modeling demonstrate that Get1, EMC3, and TMCO1 share a conserved Oxa1-like architecture. Biochemical analysis of human TMCO1, the only homolog not previously linked to membrane protein biogenesis, shows that it associates with the Sec translocon and ribosomes. These findings suggest a specific biochemical function for TMCO1 and define a superfamily of proteins-the "Oxa1 superfamily"-whose shared function is to facilitate membrane protein biogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Citation

S Andrei Anghel, Philip T McGilvray, Ramanujan S Hegde, Robert J Keenan. Identification of Oxa1 Homologs Operating in the Eukaryotic Endoplasmic Reticulum. Cell reports. 2017 Dec 26;21(13):3708-3716