Network approach of the conformational change of c-Src, a tyrosine kinase, by molecular dynamics simulation

Sci Rep. 2018 Apr 4;8(1):5673. doi: 10.1038/s41598-018-23964-5.

Abstract

Non-receptor tyrosine kinase c-Src plays a critical role in numerous cellular signalling pathways. Activation of c-Src from its inactive to the active state involves large-scale conformational changes, and is controlled by the phosphorylation state of two major phosphorylation sites, Tyr416 and Tyr527. A detailed mechanism for the entire conformational transition of c-Src via phosphorylation control of Tyr416 and Tyr527 is still elusive. In this study, we investigated the inactive-to-active conformational change of c-Src by targeted molecular dynamics simulation. Based on the simulation, we proposed a dynamical scenario for the activation process of c-Src. A detailed study of the conformational transition pathway based on network analysis suggests that Lys321 plays a key role in the c-Src activation process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • CSK Tyrosine-Protein Kinase
  • Humans
  • Molecular Dynamics Simulation*
  • Mutation*
  • Phosphorylation
  • Protein Conformation*
  • Tyrosine / chemistry
  • Tyrosine / metabolism*
  • src-Family Kinases / chemistry*
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism

Substances

  • Amino Acids
  • Tyrosine
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human