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PDBsum entry 2lyh
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DNA binding protein
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PDB id
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2lyh
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References listed in PDB file
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Key reference
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Title
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The fanconi anemia associated protein faap24 uses two substrate specific binding surfaces for DNA recognition.
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Authors
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H.Wienk,
J.C.Slootweg,
S.Speerstra,
R.Kaptein,
R.Boelens,
G.E.Folkers.
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Ref.
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Nucleic Acids Res, 2013,
41,
6739-6749.
[DOI no: ]
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PubMed id
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Abstract
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To maintain the integrity of the genome, multiple DNA repair systems exist to
repair damaged DNA. Recognition of altered DNA, including bulky adducts,
pyrimidine dimers and interstrand crosslinks (ICL), partially depends on
proteins containing helix-hairpin-helix (HhH) domains. To understand how ICL is
specifically recognized by the Fanconi anemia proteins FANCM and FAAP24, we
determined the structure of the HhH domain of FAAP24. Although it resembles
other HhH domains, the FAAP24 domain contains a canonical hairpin motif followed
by distorted motif. The HhH domain can bind various DNA substrates; using
nuclear magnetic resonance titration experiments, we demonstrate that the
canonical HhH motif is required for double-stranded DNA (dsDNA) binding, whereas
the unstructured N-terminus can interact with single-stranded DNA. Both DNA
binding surfaces are used for binding to ICL-like single/double-strand
junction-containing DNA substrates. A structural model for FAAP24 bound to dsDNA
has been made based on homology with the translesion polymerase iota.
Site-directed mutagenesis, sequence conservation and charge distribution support
the dsDNA-binding model. Analogous to other HhH domain-containing proteins, we
suggest that multiple FAAP24 regions together contribute to binding to
single/double-strand junction, which could contribute to specificity in ICL DNA
recognition.
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