POSITIONING OF Ftz–F1 DOMAIN AFFECTS ON THE ACTIVITY OF HUMAN LRH-1: MOLECULAR DYNAMICS STUDY ON HUMAN LRH-1-DNA COMPLEXES

Abstract

Molecular dynamics simulations for hLRH-1 (human liver receptor homologue-1) — DNA complexes were to investigate how the Ftz-F1 domain to regulate the transcriptional activity of hLRH-1. Comparative analyses of the three MD trajectories of hLRH-1 complexes suggest that the differential transcriptional activities of the wild-type hLRH-1, double-mutant and triple-mutant are due to alterative protein-DNA interactions. Further, the changes of position of Ftz–F1 domain can only exert limited effects on structures of the DBD (DNA binding domain), while the differences in the bound DNA's bending angles and helical parameters of key base pairs in the three systems result from the altering in distributions of the electrostatic potential surface, which varies with the positioning between the Ftz–F1 and the DBD. The disruptions or weakening of key interactions on several base pairs in the core sequence are mainly due to their distinct displacements from the helical axis in the mutant forms. So the Ftz-F1 domain can regulate the activity of the hLRH-1 by influencing conformations of the bound DNA.