Interplay between Chaperones and Protein Disorder Promotes the Evolution of Protein Networks
Figure 5
Selective protein quality control in the evolution of protein networks.
A Hubs comprise the most connected proteins in protein networks, while low connectivity bottlenecks are functionally important network nodes that connect network modules. B Hubs and bottlenecks as the most critical proteins in protein interaction networks are characterized by low ω, thus strong purifying selective pressure. Despite their generally high degree of conservation, both hubs and bottlenecks exhibit significantly higher distributions of λ. C Hubs compared to non-hubs are significantly enriched in chaperone substrates and proteins with long disordered stretches. D Deletion of the Hsp70s SSB1/2 (data obtained from [65]) results in 50% of the hubs, but less than 10% of the non-hubs to immediately aggregate. While SSB might not directly promote the evolution of hubs, it is instrumental in the homeostasis of intrinsically disordered hub proteins, thus serving as evolutionary potentiator. E Bottlenecks are significantly enriched in chaperone substrates and proteins with long disordered stretches compared to non-bottlenecks. F The Hsp70 SSB directly promotes non-conservative mutations in bottlenecks in addition to, but independent of intrinsic disorder. Significance levels are indicated as n.s. (not significant), * (p<0.05), and *** (p<0.001).