Errasti-Murugarren Ekaitz, Bartoccioni Paola, Palacín Manuel
Laboratory of Amino acid Transporters and Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, 08028 Barcelona, Spain.
CIBERER (Centro Español en Red de Biomedicina de Enfermedades Raras), 28029 Barcelona, Spain.
Membranes (Basel). 2021 Feb 22;11(2):155. doi: 10.3390/membranes11020155.
Accounting for nearly two-thirds of known druggable targets, membrane proteins are highly relevant for cell physiology and pharmacology. In this regard, the structural determination of pharmacologically relevant targets would facilitate the intelligent design of new drugs. The structural biology of membrane proteins is a field experiencing significant growth as a result of the development of new strategies for structure determination. However, membrane protein preparation for structural studies continues to be a limiting step in many cases due to the inherent instability of these molecules in non-native membrane environments. This review describes the approaches that have been developed to improve membrane protein stability. Membrane protein mutagenesis, detergent selection, lipid membrane mimics, antibodies, and ligands are described in this review as approaches to facilitate the production of purified and stable membrane proteins of interest for structural and functional studies.
膜蛋白占已知可成药靶点的近三分之二，与细胞生理学和药理学高度相关。在这方面，药理学相关靶点的结构测定将有助于新药的智能设计。由于结构测定新策略的发展，膜蛋白结构生物学领域正在经历显著增长。然而，在许多情况下，由于这些分子在非天然膜环境中固有的不稳定性，用于结构研究的膜蛋白制备仍然是一个限制步骤。本综述描述了为提高膜蛋白稳定性而开发的方法。本综述将膜蛋白诱变、去污剂选择、脂质膜模拟物、抗体和配体描述为有助于生产用于结构和功能研究的纯化且稳定的目标膜蛋白的方法。
