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.

Keywords: homodimer; interaction; interface; mode; structures; types.

Figure 1

Distribution of Interface area along the Monomer length for 2S, 3SMI and 3SDI. According to monomer length, 2S proteins fall within the range of 300, 3SMI within 400 and 3SDI within 900. This implies that 2S proteins have a small ML, 3SMI have a moderate ML, and 3SDI have a larger ML.

Figure 2

Distribution of I/T ratio for 2S, 3SMI and 3SDI. The figure implies that the I/T ratio for 2S is larger than 3SMI and 3SDI.

Figure 3

2 ‐ Dimensional representation of interfaces with large, moderate and small I/T ratio for both symmetric and asymmetric homodimers.

Figure 4

Types of interface interactions that were resolved from the information gleaned by visual inspection. There are eight types of intersubunit interaction: N (interaction only at the N terminal); C (interaction only at the C terminal); M (interaction only in the middle); NAC (interaction at both the terminals); NAM (interaction at the N terminal and in the middle); CAM (interaction at the C terminal and in the middle); NMC (interaction at both the terminals and in the middle); FL (full interaction).

Figure 5

Example of types of interfaces in 2S in accordance with large, moderate and small I/T ratios. The two vertical axes indicate residue numbers and the two horizontal axes indicate interface area.

Figure 6

Example of types of interfaces in 3SMI in accordance with large, moderate and small I/T ratios. The two vertical axes indicate residue numbers and the two horizontal axes indicate interface area.

Figure 7

Example of types of interfaces in 3SDI in accordance with large, moderate and small I/T ratios. The two vertical axes indicate residue numbers and the two horizontal axes indicate interface area.

Figure 8

Example of 3 ‐ D representation of interactions by non-inverted (1BET) and inverted (1ROP) homodimers in 2S.

Figure 9

Example of 3 ‐ D representation of interactions by non-inverted(1HQO) and inverted (1LUC) homodimers in 3SDI.

Figure 10

Example of 3 ‐ D representation of interactions by non-inverted (1DFX) homodimers in 3SMI.