Single-particle cryogenic electron microscopy structure determination for membrane proteins

Abstract

Membrane proteins are crucial to many cellular functions but are notoriously difficult for structural studies due to their instability outside their natural environment and their amphipathic nature with dual hydrophobic and hydrophilic regions. Single-particle cryogenic electron microscopy (cryo-EM) has emerged as a transformative approach, providing near–atomic-resolution structures without the need for crystallization. This review discusses advancements in cryo-EM, emphasizing membrane sample preparation and data processing techniques. It explores innovations in capturing membrane protein structures within native environments, analyzing their dynamics, binding partner interactions, lipid associations, and responses to electrochemical gradients. These developments continue to enhance our understanding of these vital biomolecules, advancing the contributions of structural biology for basic and translational biomedicine.