期刊
CELL REPORTS
卷 21, 期 13, 页码 3708-3716出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.12.006
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资金
- NIH [R21 EY026719]
- UK Medical Research Council [MC_UP_A022_1007]
- Boehringer Ingelheim Fonds Ph.D. fellowship
- NIH training grant [T32 GM007183]
- Medical Research Council [MC_UP_A022_1007] Funding Source: researchfish
- MRC [MC_UP_A022_1007] Funding Source: UKRI
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.
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