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An alternative pathway for membrane protein biogenesis at the endoplasmic reticulum.

O'Keefe, Sarah; orcid: 0000-0002-1744-0198; email: sarah.okeefe@manchester.ac.uk
; 
Zong, Guanghui; orcid: 0000-0002-7335-039X
; 
Duah, Kwabena B
; 
Andrews, Lauren E
; 
Shi, Wei Q; orcid: 0000-0001-5453-1753
; 
High, Stephen; orcid: 0000-0002-4532-8152; email: stephen.high@manchester.ac.uk
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2021-07-01
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The heterotrimeric Sec61 complex is a major site for the biogenesis of transmembrane proteins (TMPs), accepting nascent TMP precursors that are targeted to the endoplasmic reticulum (ER) by the signal recognition particle (SRP). Unlike most single-spanning membrane proteins, the integration of type III TMPs is completely resistant to small molecule inhibitors of the Sec61 translocon. Using siRNA-mediated depletion of specific ER components, in combination with the potent Sec61 inhibitor ipomoeassin F (Ipom-F), we show that type III TMPs utilise a distinct pathway for membrane integration at the ER. Hence, following SRP-mediated delivery to the ER, type III TMPs can uniquely access the membrane insertase activity of the ER membrane complex (EMC) via a mechanism that is facilitated by the Sec61 translocon. This alternative EMC-mediated insertion pathway allows type III TMPs to bypass the Ipom-F-mediated blockade of membrane integration that is seen with obligate Sec61 clients.
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Communications biology, volume 4, issue 1, page 828
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http://hdl.handle.net/10034/625468
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From Europe PMC via Jisc Publications Router
History: epub 2021-07-01, ppub 2021-07-01
Publication status: Published
Funder: Ball State University (Ball State); Grant(s): Provost Startup Award
Funder: Wellcome Trust; Grant(s): 204957/Z/16/Z
Funder: NIGMS NIH HHS; Grant(s): R15 GM116032
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