Modeling membrane proteins: the importance of cysteine amino-acids

Publication date: Available online 5 October 2019Source: Journal of Structural BiologyAuthor(s): Evgeni Grazhdankin, Michal Stepniewski, Henri XhaardAbstractComputational modeling of membrane proteins is critical to understand biochemical systems and to support chemical biology. In this work, we use a dataset of 448 non-redundant membrane protein chains to expose a “rule” that governs membrane protein structure: free cysteine thiols are not found accessible to oxidative compartments such as the extracellular space, but are rather involved in disulphide bridges. Taking as examples the 1018 three-dimensional models produced during the GPCR Dock, 2008, Dock, 2010 and 2013 competitions and 390 models for a GPCR target in CASP13, we show that this rule was not accounted for by the modeling community. We thus highlight a new direction for model development that should lead to more accurate membrane protein models, especially in the loop domains.Graphical abstract

Source: Journal of Structural Biology - October 7, 2019 Category: Biology Source Type: research