Identification of Oxa1 Homologs Operating in the Eukaryotic Endoplasmic Reticulum

Publication date: 26 December 2017
Source:Cell Reports, Volume 21, Issue 13
Author(s): S. Andrei Anghel, Philip T. McGilvray, Ramanujan S. Hegde, Robert J. Keenan
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.

Graphical abstract

Teaser

The absence of Oxa1/Alb3/YidC homologs in the eukaryotic endomembrane system has been a mystery. Now, Anghel et al. identify three ER-resident proteins, Get1, EMC3, and TMCO1, as remote homologs of Oxa1/Alb3/YidC proteins and show that TMCO1 possesses YidC-like biochemical properties. This defines the "Oxa1 superfamily" of membrane protein biogenesis factors.


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