5fhh
From Proteopedia
Structure of human Pif1 helicase domain residues 200-641
Structural highlights
Function[PIF1_HUMAN] DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. Efficiently unwinds G-quadruplex (G4) DNA structures and forked RNA-DNA hybrids. Resolves G4 structures, preventing replication pausing and double-strand breaks (DSBs) at G4 motifs. Involved in the maintenance of telomeric DNA. Inhibits telomere elongation, de novo telomere formation and telomere addition to DSBs via catalytic inhibition of telomerase. Reduces the processivity of telomerase by displacing active telomerase from DNA ends. Releases telomerase by unwinding the short telomerase RNA/telomeric DNA hybrid that is the intermediate in the telomerase reaction. Possesses an intrinsic strand annealing activity.[HAMAP-Rule:MF_03176][1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedPif1 is a conserved SF1B DNA helicase involved in maintaining genome stability through unwinding double-stranded DNAs (dsDNAs), DNA/RNA hybrids, and G quadruplex (G4) structures. Here, we report the structures of the helicase domain of human Pif1 and Bacteroides sp Pif1 (BaPif1) in complex with ADP-AlF4(-) and two different single-stranded DNAs (ssDNAs). The wedge region equivalent to the beta hairpin in other SF1B DNA helicases folds into an extended loop followed by an alpha helix. The Pif1 signature motif of BaPif1 interacts with the wedge region and a short helix in order to stabilize these ssDNA binding elements, therefore indirectly exerting its functional role. Domain 2B of BaPif1 undergoes a large conformational change upon concomitant binding of ATP and ssDNA, which is critical for Pif1's activities. BaPif1 cocrystallized with a tailed dsDNA and ADP-AlF4(-), resulting in a bound ssDNA bent nearly 90 degrees at the ssDNA/dsDNA junction. The conformational snapshots of BaPif1 provide insights into the mechanism governing the helicase activity of Pif1. Structural and Functional Insights into the Unwinding Mechanism of Bacteroides sp Pif1.,Zhou X, Ren W, Bharath SR, Tang X, He Y, Chen C, Liu Z, Li D, Song H Cell Rep. 2016 Mar 1;14(8):2030-9. doi: 10.1016/j.celrep.2016.02.008. Epub 2016, Feb 18. PMID:26904952[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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