title: Stabilizing membrane proteins through protein engineering.
abstract: Integral membrane proteins (IMPs) are crucial components of all cells but are difficult to study in vitro because they are generally unstable when removed from their native membranes using detergents. Despite the major biomedical relevance of IMPs, less than 1% of Protein Data Bank (PDB) entries are IMP structures, reflecting the technical gap between studies of soluble proteins compared to IMPs. Stability can be engineered into IMPs by inserting stabilizing mutations, thereby generating proteins that can be successfully applied to biochemical and structural studies when solubilized in detergent micelles. The identification of stabilizing mutations is not trivial, and this review will focus on the methods that have been used to identify stabilized membrane proteins, including alanine scanning and screening, directed evolution and computational design.
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors: Daniel J
authors: DJ
authors: Scott
authors: Lutz
authors: L
authors: Kummer
authors: Dirk
authors: D
authors: Tremmel
authors: Andreas
authors: A
authors: Plückthun
mesh_terms: D019020:Directed Molecular Evolution; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D016296:Mutagenesis; D015202:Protein Engineering / Q000379:methods*; D055550:Protein Stability; D012995:Solubility
chemical_list: D008565:Membrane Proteins