Understanding the specificity of a docking interaction between JNK1 and the scaffolding protein JIP1.

ABSTRACT: The up-regulation of JNK activity is associated with a number of disease states. The JNK-JIP1 interaction represents an attractive target for the inhibition of JNK-mediated signaling. In this study, molecular dynamics simulations have been performed on the apo-JNK1 and the JNK1•L-pepJIP1 and JNK1•D-pepJIP1 complexes to investigate the interaction between the JIP1 peptides and JNK1. Dynamic domain studies based on essential dynamics (ED) analysis of apo-JNK1 and the JNK1•L-pepJIP1 complex have been performed to analyze and compare details of conformational changes, hinge axes, and hinge bending regions in both structures. The activation loop, the αC helix, and the G loop are found to be highly flexible and to exhibit significant changes in dynamics upon L-pepJIP1 binding. The conformation o

SUBMITTER: Yan C 

PROVIDER: S-EPMC3042137 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature