Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients.

ABSTRACT: Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane protein complex (EMC), comprising eight conserved subunits, has emerged as a central player in this process. Yet, we have limited understanding of how EMC enables insertion and integrity of diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast and human EMC cryo-EM structures reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis. These depend on mechanistically coupled yet spatially distinct regions including two li

SUBMITTER: Miller-Vedam LE 

PROVIDER: S-EPMC7785296 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature