Giant Hub Src and Syk Tyrosine Kinase Thermodynamic Profiles Recapitulate Evolution

TL;DR

This study applies thermodynamic scaling theory to analyze the evolution of giant hub enzymes, revealing structural and evolutionary insights into tyrosine kinases across species without using adjustable parameters.

Contribution

It extends thermodynamic scaling theory to large proteins, uncovering evolutionary patterns and structural features of tyrosine kinases that explain their prominence in protein networks.

Findings

Evolution of surface roughness is first order from birds to mammals.

Identification of a septad targeting cluster in proto-oncogene tyrosine kinase.

Structural differences explain the size and network prominence of these proteins.

Abstract

Thermodynamic scaling theory, previously applied mainly to small proteins, here analyzes quantitative evolution of the titled functional network giant hub enzymes. The broad domain structure identified homologically is confirmed hydropathically using amino acid sequences only. The most surprising results concern the evolution of the tyrosine kinase globular surface roughness from avian to mammals, which is first order, compared to the evolution within mammals from rodents to humans, which is second order. The mystery of the unique amide terminal region of proto oncogene tyrosine protein kinase is resolved by the discovery there of a septad targeting cluster, which is paralleled by an octad catalytic cluster in tyrosine kinase in humans and a few other species. These results, which go far towards explaining why these proteins are among the largest giant hubs in protein interaction networks, use no adjustable parameters.