Electrostatic hot spot on DNA-binding domains mediates phosphate desolvation and the pre-organization of specificity determinant side chains.

ABSTRACT: A major obstacle towards elucidating the molecular basis of transcriptional regulation is the lack of a detailed understanding of the interplay between non-specific and specific protein-DNA interactions. Based on molecular dynamics simulations of C(2)H(2) zinc fingers (ZFs) and engrailed homeodomain transcription factors (TFs), we show that each of the studied DNA-binding domains has a set of highly constrained side chains in preset configurations ready to form hydrogen bonds with the DNA backbone. Interestingly, those domains that bury their recognition helix into the major groove are found to have an electrostatic hot spot for Cl(-) ions located on the same binding cavity as the most buried DNA phosphate. The spot is characterized by three protein hydrogen bond donors, often including tw

SUBMITTER: Temiz AN 

PROVIDER: S-EPMC2853105 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature