Lessons Learned from UvrD Helicase: Mechanism for Directional Movement

Abstract

How do molecular motors convert chemical energy to mechanical work? Helicases and nucleic acids offer simple motor systems for extensive biochemical and biophysical analyses. Atomic resolution structures of UvrD-like helicases complexed with DNA in the presence of AMPPNP, ADP·Pi, and Pi reveal several salient points that aid understanding mechano-chemical coupling. Each ATPase cycle causes two motor-domains to rotationally close and open. At a minimum, two motor-track contact points of alternating tight and loose attachment convert domain rotations to uni-directional movement. A motor is “in gear” for action only when fully in contact with its track and, if applicable, working against a load. The orientation of domain rotation relative to the track determines whether the movement is linear, spiral or circular. Motors powered by ATPases likely deliver each power stroke in two parts, before and after ATP hydrolysis. Implications of these findings for analyzing hexameric helicase, F1F0 ATPase and kinesin are discussed.

Mechanistic insights into transcription coupled DNA repair

“…It translocates in a 3′ to 5′ direction via ATP hydrolysis [58]. The function of the UvrD translocase or helicase depends on different oligomeric states acquired by the protein.…”

Genome-wide identification of SF1 and SF2 helicases from archaea

“…These are further divided into: SF1A includes UvrD-like DNA helicases with a 3'-5' polarity(Yang 2010), SF1B consists of Upf1-like DNA/RNA helicase(Azzalin et al, 2006), and Pif-1 like DNA helicase with a 5'-3' unwinding polarity(Bessler et al, 2001).SF1 families are characterized by the presence of multiple insertions within the helicase core domain. Screening of archaeal genomes for SF1 families showed the occurrence of only two families UvrD-like and Upf1-like.…”

Regulation of Transcript Elongation

“…UvrD is an integral late player in NER—it is a helicase that removes the damaged DNA fragment following processing by UvrABC (148). However, UvrD also interacts with RNAP in E. coli (33) and Bacillus subtilis (48), suggestive of a TCR model in which UvrD makes the stalled RNAP retreat from the lesion, exposing it for repair (33).…”