The cryo-EM structure of the SNX–BAR Mvp1 tetramer

• Published in: Nature communications Vol. 11; no. 1; p. 1506
• Main Authors: Sun, Dapeng, Varlakhanova, Natalia V., Tornabene, Bryan A., Ramachandran, Rajesh, Zhang, Peijun, Ford, Marijn G. J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.03.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 14/19; 14/63; 631/45/535; 631/535/1258/1259; 631/57; 631/80/313/1776; 82/16; 82/83; BAR protein; Binding Sites; Biophysics; Cell Membrane - metabolism; Complexity; Cryoelectron Microscopy - methods; Dimers; Endosomes - metabolism; Humanities and Social Sciences; Humans; Lipids; Membranes; Mitral Valve Prolapse - metabolism; Models, Molecular; multidisciplinary; N-Terminus; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Protein Domains - genetics; Protein Transport; Proteins; Saccharomyces cerevisiae - genetics; Science; Science (multidisciplinary); Sorting Nexins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15110-5

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. SNX-BAR proteins are a family of PX and BAR domain-containing proteins with pivotal roles in trafficking processes. Here authors present the cryo-EM structure of the full-length fungal SNX-BAR Mvp1, which is an autoinhibited tetramer and provides critical insight into SNX-BAR function and regulation.