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Sorting nexins (SNX) are a family of PX domain-containing proteins with pivotal roles in trafficking and signaling. SNX-BARs, which also have a curvature-generating Bin/Amphiphysin/Rvs (BAR) domain, have membrane-remodeling functions, particularly at the endosome. The minimal PX-BAR module is a dimer mediated by BAR-BAR interactions. Many SNX-BAR proteins, however, additionally have low-complexity N-terminal regions of unknown function. Here, we present the cryo-EM structure of the full-length SNX-BAR Mvp1, which is an autoinhibited tetramer. The tetramer is a dimer of dimers, wherein the membrane-interacting BAR surfaces are sequestered and the PX lipid-binding sites are occluded. The N-terminal low-complexity region of Mvp1 is essential for tetramerization. Mvp1 lacking its N-terminus is dimeric and exhibits enhanced membrane association. Membrane binding and remodeling by Mvp1 therefore requires unmasking of the PX and BAR domain lipid-interacting surfaces. This work reveals a tetrameric configuration of a SNX-BAR protein that provides critical insight into SNX-BAR function and regulation.

Original publication

DOI

10.1038/s41467-020-15110-5

Type

Journal article

Journal

Nature communications

Publication Date

20/03/2020

Volume

11

Addresses

Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.

Keywords

Cell Membrane, Endosomes, Humans, Saccharomyces cerevisiae, Mitral Valve Prolapse, Nerve Tissue Proteins, Cryoelectron Microscopy, Biophysics, Binding Sites, Protein Transport, Models, Molecular, Sorting Nexins, Protein Domains