5W7Y

Crystal Structure of FHA domain of human APLF in complex with XRCC1 monophosphorylated mutated peptide

5W7Y の概要

• エントリーDOI: 10.2210/pdb5w7y/pdb
• 分子名称: Aprataxin and PNK-like factor, DNA repair protein XRCC1 (3 entities in total)
• 機能のキーワード: scaffold protein, dna repair, nhej, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: Q8IW19 P18887
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 25765.30

構造登録者

Pedersen, L.C.,Kim, K.,London, R.E. (登録日: 2017-06-21, 公開日: 2018-05-02, 最終更新日: 2024-10-16)

主引用文献

Kim, K.,Pedersen, L.C.,Kirby, T.W.,DeRose, E.F.,London, R.E.
Characterization of the APLF FHA-XRCC1 phosphopeptide interaction and its structural and functional implications.
Nucleic Acids Res., 45:12374-12387, 2017

PubMed Abstract: Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using crystallographic, NMR, and fluorescence polarization studies. The FHA-FBM interactions exhibit significant pH dependence in the physiological range as a consequence of the atypically high pK values of the phosphoserine and phosphothreonine residues and the preference for a dianionic charge state of FHA-bound pThr. These high pK values are characteristic of the polyanionic peptides typically produced by CK2 phosphorylation. Binding affinity is greatly enhanced by residues flanking the crystallographically-defined recognition motif, apparently as a consequence of non-specific electrostatic interactions, supporting the role of XRCC1 in nuclear cotransport of APLF. The FHA domain-dependent interaction of XRCC1 with APLF joins repair scaffolds that support single-strand break repair and non-homologous end joining (NHEJ). It is suggested that for double-strand DNA breaks that have initially formed a complex with PARP1 and its binding partner XRCC1, this interaction acts as a backup attempt to intercept the more error-prone alternative NHEJ repair pathway by recruiting Ku and associated NHEJ factors.

PubMed: 29059378
DOI: 10.1093/nar/gkx941

実験手法

X-RAY DIFFRACTION (2.1 Å)