Chien Chih-Ta, Maduke Merritt, Chiu Wah
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA.
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Curr Opin Struct Biol. 2025 Jun;92:103047. doi: 10.1016/j.sbi.2025.103047. Epub 2025 Apr 13.
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.
膜蛋白对许多细胞功能至关重要，但由于其在天然环境之外的不稳定性以及具有疏水和亲水双重区域的两亲性，其结构研究一直非常困难。单颗粒低温电子显微镜（cryo-EM）已成为一种变革性方法，无需结晶即可提供近原子分辨率的结构。本综述讨论了低温电子显微镜的进展，重点强调了膜样品制备和数据处理技术。它探讨了在捕获天然环境中的膜蛋白结构、分析其动力学、结合伴侣相互作用、脂质关联以及对电化学梯度的响应方面的创新。这些进展不断增进我们对这些重要生物分子的理解，推动结构生物学对基础和转化生物医学的贡献。
