title: Comparison of bacteriophage T4 UvsX and human Rad51 filaments suggests that RecA-like polymers may have evolved independently.
abstract: The UvsX protein from bacteriophage T4 is a member of the RecA/Rad51/RadA family of recombinases active in homologous genetic recombination. Like RecA, Rad51 and RadA, UvsX forms helical filaments on DNA. We have used electron microscopy and a novel method for image analysis of helical filaments to show that UvsX-DNA filaments exist in two different conformations: an ADP state and an ATP state. As with RecA protein, these two states have a large difference in pitch. Remarkably, even though UvsX is only weakly homologous to RecA, both UvsX filament states are more similar to the RecA crystal structure than are RecA-DNA filaments. We use this similarity to fit the RecA crystal structure into the UvsX filament, and show that two of the three previously described blocks of similarity between UvsX and RecA are involved in the subunit-subunit interface in both the UvsX filament and the RecA crystal filament. Conversely, we show that human Rad51-DNA filaments have a different subunit-subunit interface than is present in the RecA crystal, and this interface involves two blocks of sequence similarity between Rad51 and RecA that do not overlap with those found between UvsX and RecA. This suggests that helical filaments in the RecA/Rad51/RadA family may have arisen from convergent evolution, with a conserved core structure that has assembled into multimeric filaments in a number of different ways.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, VA 22908-0733, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: M S
authors.initials: MS
authors.lastname: VanLoock
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: E H
authors.initials: EH
authors.lastname: Egelman
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017607:Aluminum Compounds / Q000378:metabolism; D017122:Bacteriophage T4 / Q000737:chemistry; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D019143:Evolution, Molecular; D005459:Fluorides / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D051135:Rad51 Recombinase; D011938:Rec A Recombinases / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure*; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D017607:Aluminum Compounds; D001704:Biopolymers; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; C092863:UvsX protein, Enterobacteria phage T4; D014764:Viral Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D011938:Rec A Recombinases; D005459:Fluorides; C032311:aluminum fluoride