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

Nat Commun. 2020 Mar 20;11(1):1506. doi: 10.1038/s41467-020-15110-5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Biophysics
  • Cell Membrane / metabolism
  • Cryoelectron Microscopy / methods*
  • Endosomes / metabolism
  • Humans
  • Mitral Valve Prolapse / metabolism*
  • Models, Molecular
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Domains / genetics
  • Protein Transport
  • Saccharomyces cerevisiae / genetics
  • Sorting Nexins / metabolism*

Substances

  • Nerve Tissue Proteins
  • Sorting Nexins
  • amphiphysin

Supplementary concepts

  • Mitral Valve Prolapse, Myxomatous 1