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Architecture and mechanism of metazoan retromer:SNX3 tubular coat assembly

Published version
Peer-reviewed

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Type

Article

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Authors

Briggs, John 
Morado, Dustin 
Kovtun, Oleksiy 

Abstract

Retromer is a master regulator of cargo retrieval from endosomes, which is critical for many cellular processes including signalling, immunity, neuroprotection and virus infection. The retromer core (VPS26/VPS29/VPS35) is present on cargo-transporting, tubular carriers along with a range of sorting nexins. Here, we elucidate the structural basis of membrane tubulation and coupled cargo recognition by metazoan and fungal retromer coats assembled with the non-BAR sorting nexin SNX3 using cryo-electron tomography. The retromer core retains its arched, scaffolding structure but changes its mode of membrane recruitment when assembled with different SNX adaptors allowing cargo recognition at subunit interfaces. Thus membrane bending and cargo incorporation can be modulated to allow retromer to traffic cargoes along different cellular transport routes.

Description

Keywords

3101 Biochemistry and Cell Biology, 31 Biological Sciences, Infectious Diseases, 2 Aetiology, 2.1 Biological and endogenous factors

Journal Title

Science Advances

Conference Name

Journal ISSN

2375-2548
2375-2548

Volume Title

Publisher

American Association for the Advancement of Science (AAAS)
Sponsorship
Wellcome Trust (202905/Z/16/Z)
Wellcome Trust (207455/Z/17/Z)
Wellcome Trust (206171/Z/17/Z)
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