Vesicle Picker: A tool for efficient identification of membrane protein complexes in vesicles

J Struct Biol. 2024 Dec;216(4):108148. doi: 10.1016/j.jsb.2024.108148. Epub 2024 Oct 30.

Abstract

Electron cryomicroscopy (cryo-EM) has recently allowed determination of near-atomic resolution structures of membrane proteins and protein complexes embedded in lipid vesicles. However, particle selection from electron micrographs of these vesicles can be challenging due to the strong signal contributed from the lipid bilayer. This challenge often requires iterative and laborious particle selection workflows to generate a dataset of high-quality particle images for subsequent analysis. Here we present Vesicle Picker, an open-source program built on the Segment Anything model. Vesicle Picker enables automatic identification of vesicles in cryo-EM micrographs with high recall and precision. It then exhaustively selects all potential particle locations, either at the perimeter or uniformly over the surface of the projection of the vesicle. The program is designed to interface with cryoSPARC, which performs both upstream micrograph processing and downstream single particle image analysis. We demonstrate Vesicle Picker's utility by determining a high-resolution map of the vacuolar-type ATPase from micrographs of native synaptic vesicles (SVs) and identifying an additional protein or protein complex in the SV membrane.

Keywords: Cryo-EM; Membrane proteins; Particle selection; Segment Anything; Single particle analysis; Vesicles.

MeSH terms

  • Animals
  • Cryoelectron Microscopy* / methods
  • Image Processing, Computer-Assisted / methods
  • Lipid Bilayers / chemistry
  • Membrane Proteins* / chemistry
  • Membrane Proteins* / ultrastructure
  • Software
  • Synaptic Vesicles* / chemistry
  • Synaptic Vesicles* / metabolism
  • Synaptic Vesicles* / ultrastructure
  • Vacuolar Proton-Translocating ATPases / chemistry
  • Vacuolar Proton-Translocating ATPases / metabolism
  • Vacuolar Proton-Translocating ATPases / ultrastructure

Substances

  • Membrane Proteins
  • Lipid Bilayers
  • Vacuolar Proton-Translocating ATPases