Types of interfaces for homodimer folding and binding

Abstract

Homodimers have a role in catalysis and regulation through the formation of stable interfaces. These interfaces are formed through different folding mechanisms such as 2-state without stable intermediate (2S), 3-state with monomer intermediate (3SMI) and 3-state with dimer intermediate (3SDI). Therefore, it is of interest to understand folding mechanism using structural features at the interfaces. Several studies have documented the significance of structural features for the understanding of homodimer folding mechanisms. However, the known features provide limited information for understanding homodimer folding mechanisms. Hence, we created an extended dataset of 47 homodimers (twenty eight 2S, twelve 3SMI and seven 3SDI) to examine the types of interfaces in protein homodimers. 2S are usually small sized, 3SMI are often medium sized and 3SDI often exist as large sized proteins. The ratio of interface to total (I/T) residue is large in 2S and small in 3SMI and 3SDI. Hence, we used I/T measure to group 2S, 3SMI and 3SDI into categories with large I/T (≫ 50%), moderate I/T (50 - 25%) and small I/T (≪ 25%) interfaces. The grouping is further sub-grouped based on the type of physical interaction visualized at the interface using representations in two dimensions (2D). 2D representation of the interface shows eight different forms of interactions in these homodimers. 2S homodimers frequently have large I/T and thus, utilize the entire protein structure in the formation of the interface where the individual subunits are heavily inter communicated with each other. This is not true in the case of 3SMI and 3SDI. 3SMI subunits usually interact with each other at the interface with a gentle touch-like contact and hence, they have low I/T ratio. 3SDI are often quite different in interaction compared to 3SMI and their subunits do deeply interact at the interface with only one part of the surface and hence also having low I/T ratio.

Improving accuracy of protein contact prediction using balanced network deconvolution

“…Long-range residue-residue contacts are the most important to protein structure determinations, but they are usually more difficult for predictions as shown in the recent CASP competitions. 15,24,25 In previous studies, there are different definitions of long-range contacts, for example, residue contacts with sequence separation larger than 23, 20, 15, or 8. 7 BND is also found to be significantly helpful for mining the long-range contacts (Table I).…”

Geometrical and electro-static determinants of protein-protein interactions

“…protein-protein complex, protein-DNA complex, protein-RNA complex, protein-membrane complex, protein-lipid complex, protein-carbohydrate complex, and others). In protein-protein complexes, the interaction of two or more proteins is very specific and is usually characterized by only a small subset of their surfaces [12][13][14][15]. Only those sites which own the proper binding features participate in the formation of PPCs [16][17][18][19][20] (Supplementary Figure 1).…”