Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
DNA Repair (Amst)
2020 Jan 01;85:102739. doi: 10.1016/j.dnarep.2019.102739.
Show Gene links
Show Anatomy links
Ligand binding characteristics of the Ku80 von Willebrand domain.
Kim K
,
Min J
,
Kirby TW
,
Gabel SA
,
Pedersen LC
,
London RE
.
???displayArticle.abstract???
The N-terminal von Willebrand domain of Ku80 supports interactions with a Ku binding motif (KBM) that has been identified in at least three other DNA repair proteins: the non-homologous end joining (NHEJ) scaffold APLF, the modulator of retrovirus infection, MRI, and the Werner syndrome protein (WRN). A second, more recently identified Ku binding motif present in XLF and several other proteins (KBMX) has also been reported to interact with this domain. The isolated Ku80 von Willebrand antigen domain (vWA) from Xenopus laevis has a sequence that is 60% identical with the human domain, is readily expressed and has been used to investigate these interactions. Structural characterization of the complexes formed with the KBM motifs in human APLF, MRI, and WRN identify a conserved binding site that is consistent with previously-reported mutational studies. In contrast with the KBM binding site, structural studies indicate that the KBMX site is occluded by a distorted helix. Fluorescence polarization and 19F NMR studies of a fluorinated XLF C-terminal peptide failed to indicate any interaction with the frog vWA. It was hypothesized that availability of this binding site is conditional, i.e., dependent on specific experimental conditions or other repair factors to make the site available for binding. Modulating the fraction of KBMX-accessible binding site mutationally demonstrated that the more open site is capable of binding the KBMXXLF motif peptide. It is suggested that the conditional nature of KBMX binding limits formation of non-productive complexes so that activation-dependent site availability can more optimally support advancing the synapsis process.
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010, Pubmed
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010,
Pubmed
Agarwal,
Isolation, characterization, and genetic complementation of a cellular mutant resistant to retroviral infection.
2006,
Pubmed
Ahel,
The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.
2006,
Pubmed
Andres,
A human XRCC4-XLF complex bridges DNA.
2012,
Pubmed
Anthis,
Sequence-specific determination of protein and peptide concentrations by absorbance at 205 nm.
2013,
Pubmed
Aravind,
Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system.
2001,
Pubmed
Arnoult,
Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN.
2017,
Pubmed
Bhargava,
C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains.
2018,
Pubmed
Boulton,
Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing.
1998,
Pubmed
Chen,
Structural Insights into Yeast Telomerase Recruitment to Telomeres.
2018,
Pubmed
Das,
Crystallography and the design of anti-AIDS drugs: conformational flexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors.
2005,
Pubmed
Davis,
DNA double strand break repair via non-homologous end-joining.
2013,
Pubmed
Emsley,
Coot: model-building tools for molecular graphics.
2004,
Pubmed
Fell,
The Ku heterodimer: function in DNA repair and beyond.
2015,
Pubmed
Gabel,
XRCC1 interaction with the REV1 C-terminal domain suggests a role in post replication repair.
2013,
Pubmed
Grundy,
One ring to bring them all--the role of Ku in mammalian non-homologous end joining.
2014,
Pubmed
Grundy,
APLF promotes the assembly and activity of non-homologous end joining protein complexes.
2013,
Pubmed
Grundy,
The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins.
2016,
Pubmed
Hsiou,
Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms.
1996,
Pubmed
Hung,
MRI Is a DNA Damage Response Adaptor during Classical Non-homologous End Joining.
2018,
Pubmed
Karmakar,
Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus.
2002,
Pubmed
Khan,
Lowering the entropic barrier for binding conformationally flexible inhibitors to enzymes.
1998,
Pubmed
Kirby,
Nuclear Localization of the DNA Repair Scaffold XRCC1: Uncovering the Functional Role of a Bipartite NLS.
2015,
Pubmed
Li,
Functional interaction between Ku and the werner syndrome protein in DNA end processing.
2000,
Pubmed
Malkov,
A reexamination of the propensities of amino acids towards a particular secondary structure: classification of amino acids based on their chemical structure.
2008,
Pubmed
McCoy,
Phaser crystallographic software.
2007,
Pubmed
Nemoz,
XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining.
2018,
Pubmed
Otwinowski,
Processing of X-ray diffraction data collected in oscillation mode.
1997,
Pubmed
Rodgers,
The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1.
1995,
Pubmed
Ropars,
Structural characterization of filaments formed by human Xrcc4-Cernunnos/XLF complex involved in nonhomologous DNA end-joining.
2011,
Pubmed
Rost,
PHD--an automatic mail server for protein secondary structure prediction.
1994,
Pubmed
Rulten,
Non-homologous end joining: Common interaction sites and exchange of multiple factors in the DNA repair process.
2017,
Pubmed
Shirodkar,
Identification and functional characterization of a Ku-binding motif in aprataxin polynucleotide kinase/phosphatase-like factor (APLF).
2013,
Pubmed
Slavoff,
A human short open reading frame (sORF)-encoded polypeptide that stimulates DNA end joining.
2014,
Pubmed
Studier,
Protein production by auto-induction in high density shaking cultures.
2005,
Pubmed
Tumbale,
Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.
2014,
Pubmed
Walker,
Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair.
2001,
Pubmed
Wu,
Non-homologous end-joining partners in a helical dance: structural studies of XLF-XRCC4 interactions.
2011,
Pubmed
Yano,
Functional significance of the interaction with Ku in DNA double-strand break recognition of XLF.
2011,
Pubmed
Yin,
Cryo-EM structure of human DNA-PK holoenzyme.
2017,
Pubmed
Zhao,
The essential elements for the noncovalent association of two DNA ends during NHEJ synapsis.
2019,
Pubmed
