How many protein-protein interactions types exist in nature?

Abstract

"Protein quaternary structure universe" refers to the ensemble of all protein-protein complexes across all organisms in nature. The number of quaternary folds thus corresponds to the number of ways proteins physically interact with other proteins. This study focuses on answering two basic questions: Whether the number of protein-protein interactions is limited and, if yes, how many different quaternary folds exist in nature. By all-to-all sequence and structure comparisons, we grouped the protein complexes in the protein data bank (PDB) into 3,629 families and 1,761 folds. A statistical model was introduced to obtain the quantitative relation between the numbers of quaternary families and quaternary folds in nature. The total number of possible protein-protein interactions was estimated around 4,000, which indicates that the current protein repository contains only 42% of quaternary folds in nature and a full coverage needs approximately a quarter century of experimental effort. The results have important implications to the protein complex structural modeling and the structure genomics of protein-protein interactions.

Figure 1. Graphical representation of all non-redundant protein-protein complex structures in the PDB.

Each node represents a known complex structure and two nodes are connected by an edge if the rTM-score between the two structures is >0.5. The orphan nodes are shown in black while nodes which are connected by at least one edge shown in yellow. Representative examples from eight largest clusters are listed together with the protein name.

Figure 2. Histogram of complex structural clusters versus size of the clusters.

The solid curve is the fitting result from Eq. 12. Inset: the same data drawn in logarithm scale.

Figure 3. The estimated number of quaternary folds versus the number of quaternary families in nature.

The solid curve is the fitting from Eq. 13 and dotted line indicates the number of quaternary families following Orengo et al. estimation.

Figure 4. The number of new complex structure entries deposited per year in the PDB.

Data are presented in terms of unique structures (sequence identity <90%), families (mapped with unique Pfam families), and folds (rTM-score <0.5).