Conformational Dynamics and Allostery in E2:E3 Interactions Drive Ubiquitination: gp78 and Ube2g2.
|Title||Conformational Dynamics and Allostery in E2:E3 Interactions Drive Ubiquitination: gp78 and Ube2g2.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Chakrabarti KS, Li J, Das R, R Byrd A|
|Date Published||2017 Apr 13|
Conformational dynamics plays a fundamental role in molecular recognition and activity in enzymes. The ubiquitin-conjugating enzyme (E2) Ube2g2 functions with the ubiquitin ligase (E3) gp78 to assemble poly-ubiquitin chains on target substrates. Two domains in gp78, RING and G2BR, bind to two distant regions of Ube2g2, and activate it for ubiquitin (Ub) transfer. G2BR increases the affinity between the RING and Ube2g2 by 50-fold, while the RING catalyzes the transfer of Ub from the Ube2g2∼Ub conjugate. How G2BR and RING activate Ube2g2 is unclear. In this work, conformational dynamics in Ube2g2 revealed a clear correlation of binding G2BR and RING with the sequential progression toward Ub transfer. The interrelationship of the existence and exchange between ground and excited states leads to a dynamic energy landscape model, in which redistribution of populations contributes to allostery and activation. These findings provide insight into gp78's modulation of conformational exchange in Ube2g2 to stimulate ubiquitination.