2M9N

Solution Structure of (HhH)2 domain of human FAAP24

2M9N の概要

• エントリーDOI: 10.2210/pdb2m9n/pdb
• 関連するPDBエントリー: 2M9M
• NMR情報: BMRB: 19303
• 分子名称: Fanconi anemia-associated protein of 24 kDa (1 entity in total)
• 機能のキーワード: fanconi anemia, faap24, (hhh)2 domain, dna binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9BTP7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6772.76

構造登録者

Wu, F.,Han, X.,Shi, C.,Gong, W.,Tian, C. (登録日: 2013-06-18, 公開日: 2013-09-18, 最終更新日: 2024-05-15)

主引用文献

Wang, Y.,Han, X.,Wu, F.,Leung, J.W.,Lowery, M.G.,Do, H.,Chen, J.,Shi, C.,Tian, C.,Li, L.,Gong, W.
Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response.
Cell Res., 23:1215-1228, 2013

PubMed Abstract: The FANCM/FAAP24 heterodimer has distinct functions in protecting cells from complex DNA lesions such as interstrand crosslinks. These functions rely on the biochemical activity of FANCM/FAAP24 to recognize and bind to damaged DNA or stalled replication forks. However, the DNA-binding activity of this complex was not clearly defined. We investigated how FAAP24 contributes to the DNA-interacting functions of the FANCM/FAAP24 complex by acquiring the N-terminal and C-terminal solution structures of human FAAP24. Modeling of the FAAP24 structure indicates that FAAP24 may possess a high affinity toward single-stranded DNA (ssDNA). Testing of various FAAP24 mutations in vitro and in vivo validated this prediction derived from structural analyses. We found that the DNA-binding and FANCM-interacting functions of FAAP24, although both require the C-terminal (HhH)2 domain, can be distinguished by segregation-of-function mutations. These results demonstrate dual roles of FAAP24 in DNA damage response against crosslinking lesions, one through the formation of FANCM/FAAP24 heterodimer and the other via its ssDNA-binding activity required in optimized checkpoint activation.

PubMed: 23999858
DOI: 10.1038/cr.2013.124

実験手法

SOLUTION NMR