title: Structural basis for transcription-coupled repair: the N terminus of Mfd resembles UvrB with degenerate ATPase motifs.
abstract: The transcription repair coupling factor Mfd removes stalled RNA polymerase from DNA lesions and links transcription to UvrABC-dependent nucleotide excision repair in prokaryotes. We report the 2.1A crystal structure of the UvrA-binding N terminus (residues 1-333) of Escherichia coli Mfd (Mfd-N). Remarkably, Mfd-N reveals a fold that resembles the three N-terminal domains of the repair enzyme UvrB. Domain 1A of Mfd adopts a typical RecA fold, domain 1B matches the damage-binding domain of the UvrB, and domain 2 highly resembles the implicated UvrA-binding domain of UvrB. However, Mfd apparently lacks a functional ATP-binding site and does not contain the DNA damage-binding motifs of UvrB. Thus, our results suggest that Mfd might form a UvrA recruitment factor at stalled transcription complexes that architecturally but not catalytically resembles UvrB.
authors.affiliation: Gene Center and Department of Chemistry and Biochemistry, University of Munich (LMU), Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Assenmacher
authors.forename: Katja
authors.initials: K
authors.lastname: Wenig
authors.forename: Alfred
authors.initials: A
authors.lastname: Lammens
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Hopfner
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011938:Rec A Recombinases / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D014157:Transcription Factors; C058093:UvrB protein, E coli; C072103:transcription repair coupling factor protein, Bacteria; D000255:Adenosine Triphosphate; D011938:Rec A Recombinases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases