Interaction modes at protein hetero-dimer interfaces

Abstract

Hetero dimer (different monomers) interfaces are involved in catalysis and regulation through the formation of interface active sites. This is critical in cell and molecular biology events. The physical and chemical factors determining the formation of the interface active sites is often large in numbers. The combined role of interacting features is frequently combinatorial and additive in nature. Therefore, it is important to determine the physical and chemical features of such interactions. A number of such features have been documented in literature since 1975. However, the use of such interaction features in the prediction of interaction partners and sites given their sequences is still a challenge. In a non-redundant dataset of 156 hetero-dimer structures determined by X-ray crystallography, the interacting partners are often varying in size and thus, size variation between subunits is an important factor in determining the mode of interface formation. The size of protein subunits interacting are either small-small, largelarge, medium-medium, large-small, large-medium and small-medium. It should also be noted that the interface formed between subunits have physical interactions at N terminal (N), C terminal (C) and middle (M) region of the protein with reference to their sequences in one dimension. These features are believed to have application in the prediction of interaction partners and sites from sequences. However, the use of such features for interaction prediction from sequence is not currently clear.

In silico analysis of protein-protein interfaces: Tools and approaches

“…Bahadur et al (2004) used interface area, crystal packing, residue propensities and hydrophobic interaction energy to measure speci ic interfaces (70 protein-protein complexes) and nonspeci ic interfaces (188 monomeric proteins) and observed that the atomic packing is less compact in non-speci ic interfaces in comparison to the speci ic interfaces. Vaishnavi et al (2010) reported that the variation in the size of interacting protein partners to be a signi icant factor in deciding the mode of interaction using 156 heterodimer protein Bahadur et al (2004) used interface area, crystal packing, residue propensities and hydrophobic interaction energy to measure speci ic interfaces (70 proteinprotein complexes) and non-speci ic interfaces (188 monomeric proteins) and observed that the atomic packing is less compact in non-speci ic interfaces in comparison to the speci ic interfaces. Vaishnavi et al (2010) reported that the variation in the size of interacting protein partners to be a signi icant factor in deciding the mode of interaction using 156 heterodimer protein interfaces.…”

“…Vaishnavi et al (2010) reported that the variation in the size of interacting protein partners to be a signi icant factor in deciding the mode of interaction using 156 heterodimer protein Bahadur et al (2004) used interface area, crystal packing, residue propensities and hydrophobic interaction energy to measure speci ic interfaces (70 proteinprotein complexes) and non-speci ic interfaces (188 monomeric proteins) and observed that the atomic packing is less compact in non-speci ic interfaces in comparison to the speci ic interfaces. Vaishnavi et al (2010) reported that the variation in the size of interacting protein partners to be a signi icant factor in deciding the mode of interaction using 156 heterodimer protein interfaces. Conte et al (1999) analyzed 75 protein-protein interfaces with known structure and observed small interfaces with small conformational changes and large interfaces with large conformational changes and also reported that some interfaces are predominantly polar and some are non-polar with charged residues above average.…”

Geometrical and electro-static determinants of protein-protein interactions

“…This specificity and accuracy of the interacting proteins determines the fate of cells [1][2][3]. Proteinprotein interactions (PPIs) form the very basis for all biological processes, such as signal transduction, material /energy transport, metabolic reactions, regulation of gene expression, cellular growth and proliferation [3][4][5][6]. These interactions form the fundamentals of the intracellular / intercellular communications [7].…”

Insights from the structural analysis of protein heterodimer interfaces

“…protein size, interface size, interface area, gap volume, gap index, planarity, hydrogen bonds, salt bridges, residue propensity, etc.) based on mean statistics for large datasets [ 8 , 9 , 10 , 11 , 12 , 13 ]. Online web servers are also available for studying PPI using these features [ 14 , 15 , 16 ].…”