Computational Characterization of Structural & Thermodynamic Properties of Beta-barrel Membrane Proteins
MetadataShow full item record
Beta-barrel membrane proteins are found in the outer membrane of gram-negative bacteria, mitochondria, and chloroplasts. They carry out diverse biological functions, including pore formation, membrane anchoring, enzyme activity, and are often responsible for bacterial virulence. By using a novel statistical mechanical approach that allows the computation of full partition function and thermodynamic properties such as melting temperature, I have developed a method to identify weakly stable regions in the transmembrane (TM) domain and discovered that out-clamps, in-plugs, protein-lipid interactions and oligomerization are four general mechanisms stabilizing the beta-barrel membrane proteins. This method can predict the oligomerization state and can identify the interfaces of protein-protein interaction in the TM region. It is based on fundamental physical principles and only sequence information alone is required. In a blind test, oligomerization state of beta-barrel membrane proteins can be predicted with 100% accuracy, and the protein-protein interfaces can be identified with 86% accuracy. Experiments involving site-directed mutagenesis, SDS-PAGE, CD spectroscopy, tryptophan flourescence, thermal and chemical denaturation have confirmed predictions of important residues in the protein-protein interaction interface of OmpF, VDAC, and Tom40 proteins. Difficulties in experimental determination of structures of beta-barrel membrane proteins have increased the importance of computational modeling for these proteins. I have further developed a computational method called 3D-SPoT for predicting three dimensional structures of the TM domains of beta-barrel membrane proteins. Using a combinatorial model, this method can construct 3D structures of the TM region of beta-barrel membrane proteins using sequence information only. The average RMSD between predicted and true TM region is about 4 Angstrom. This method successfully predicted the structure of the TM domain of VDAC, a mitochondrial membrane protein with no known homologous structure. I also describe a framework to study the assembly of multi-chain proteins into a single beta-barrel structure.
SubjectBeta-barrel membrane proteins
weakly stable regions
the protein-protein interactions
3D Structure Predictor of Transmembrane β-Barrels
Outermembrane protein F
Translocase of the outer choloroplast protein 75
Translocase of the outermitochondrial membrane protein 40
Voltage Dependent Anion Channel
Date available in INDIGO2012-12-10T16:36:17Z
Showing items related by title, author, creator and subject.
Chugani, Sudha A. (1998)
Abraham, Sherwin (2014-12-04)
Protein species and moonlighting proteins: Very small changes in a protein's covalent structure can change its biochemical function Jeffery, C.J. (Elsevier, 2016-02)In the past few decades, hundreds of moonlighting proteins have been identified that perform two or more distinct and physiologically relevant biochemical or biophysical functions that are not due to gene fusions, multiple ...