3KT9

Aprataxin FHA Domain

3KT9 の概要

• エントリーDOI: 10.2210/pdb3kt9/pdb
• 分子名称: Aprataxin (2 entities in total)
• 機能のキーワード: fha domain, beta sandwich, beta sheet, amp hydrolase, alternative splicing, disease mutation, dna damage, dna repair, dna-binding, hydrolase, metal-binding, neurodegeneration, nucleus, zinc, zinc-finger
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11789.76

構造登録者

Cherry, A.L.,Smerdon, S.J. (登録日: 2009-11-24, 公開日: 2010-01-26, 最終更新日: 2024-02-21)

主引用文献

Becherel, O.J.,Jakob, B.,Cherry, A.L.,Gueven, N.,Fusser, M.,Kijas, A.W.,Peng, C.,Katyal, S.,McKinnon, P.J.,Chen, J.,Epe, B.,Smerdon, S.J.,Taucher-Scholz, G.,Lavin, M.F.
CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response.
Nucleic Acids Res., 38:1489-1503, 2010

PubMed Abstract: Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1.

PubMed: 20008512
DOI: 10.1093/nar/gkp1149

実験手法

X-RAY DIFFRACTION (1.65 Å)