PDBsum entry 2lyh

DNA binding protein

PDB id: 2lyh

Contents

Protein chain

75 a.a.

PDB id:

2lyh

Name:

DNA binding protein

Title:

Structure of faap24 residues 141-215

Structure:

Fanconi anemia-associated protein of 24 kda. Chain: a. Fragment: unp residues 141-215. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: c19orf40, faap24. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

H.Wienk,J.Slootweg,R.Kaptein,R.Boelens,G.E.Folkers

Key ref:

H.Wienk et al. (2013). The Fanconi anemia associated protein FAAP24 uses two substrate specific binding surfaces for DNA recognition. Nucleic Acids Res, 41, 6739-6749. PubMed id: 23661679 DOI: 10.1093/nar/gkt354

Date:

18-Sep-12 Release date: 01-May-13

Protein chain

Q9BTP7  (FAP24_HUMAN) -  Fanconi anemia core complex-associated protein 24 from Homo sapiens

Seq: 215 a.a.

Struc: 75 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1093/nar/gkt354

Nucleic Acids Res 41:6739-6749 (2013)

PubMed id: 23661679

The Fanconi anemia associated protein FAAP24 uses two substrate specific binding surfaces for DNA recognition.

H.Wienk, J.C.Slootweg, S.Speerstra, R.Kaptein, R.Boelens, G.E.Folkers.

ABSTRACT

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.