Predicting Strained Regions for Folding and Protein-Protein Interaction in Bacterial Outer Membranes

Abstract

Beta-barrel membrane proteins are found in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. Exposed on the surface of bacterial cells, many beta-barrel proteins are initial sites of attachment by bacteriophages and bacterial toxins. Little information is known on the stability of local regions of these membrane proteins, and how they interact with each other. We have developed a model to quantify energy level of transmembrane strands in beta-barrel membrane proteins. We showed that our predictions on PagP are consistent with recent experimental NMR studies of protein dynamics [1] and mutant studies of folding stability [2]. We further found that the strands located in the interfaces of protein-protein interactions are considerably less stable by our model We have further developed a method to predict interface of protein-protein interaction of beta-barrel membrane proteins. In a data set of 25 beta-barrel membrane protein structures with less than 32% pairwise sequence identity, we can predict whether the protein will form a monomeric or multimeric structure with 91% accuracy and identify the protein-protein interaction interface with an accuracy of 86% in leave one out tests using sequence information only. We also report results of predicting genome-wide protein-protein interaction in bacterial outer membranes. [1] Evanics F., Hwang P.M., Cheng Y., Kay L.E. and Prosser R.S. (2006). Topology of Outer-Membrane Enzyme: Measuring Oxygen and Water Contacts in Solution NMR Studies of PagP. J. Am. Chem. Soc., 128, 8256-8264. [2] Huysmans G.H.M., Radford S.E., Brockwell D.J. and Baldwin S.A. (2007). The N-terminal Helix is a Post-assembly Clamp in the Bacterial Outer Membrane Protein PagP. J. Mol. Biol., 373, 529-540.