2LD1

Structures and chemical shift assignments for the ADD domain of the ATRX protein

2LD1 の概要

• エントリーDOI: 10.2210/pdb2ld1/pdb
• NMR情報: BMRB: 15001
• 分子名称: Transcriptional regulator ATRX, ZINC ION (2 entities in total)
• 機能のキーワード: hydrolase, metal binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P46100
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16470.83

構造登録者

Neuhaus, D.,Yang, J. (登録日: 2011-05-13, 公開日: 2011-06-08, 最終更新日: 2024-05-01)

主引用文献

Argentaro, A.,Yang, J.C.,Chapman, L.,Kowalczyk, M.S.,Gibbons, R.J.,Higgs, D.R.,Neuhaus, D.,Rhodes, D.
Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.
Proc.Natl.Acad.Sci.USA, 104:11939-11944, 2007

PubMed Abstract: The chromatin-associated protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation associated with alpha-thalassemia. Half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX. This region was named the ATRX-DNMT3-DNMT3L (ADD) domain, based on sequence homology with a family of DNA methyltransferases. Here, we report the solution structure of the ADD domain of ATRX, which consists of an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal alpha-helix that pack together to form a single globular domain. Interestingly, the alpha-helix of the GATA-like finger is exposed and highly basic, suggesting a DNA-binding function for ATRX. The disease-causing mutations fall into two groups: the majority affect buried residues and hence affect the structural integrity of the ADD domain; another group affects a cluster of surface residues, and these are likely to perturb a potential protein interaction site. The effects of individual point mutations on the folding state and stability of the ADD domain correlate well with the levels of mutant ATRX protein in patients, providing insights into the molecular pathophysiology of ATR-X syndrome.

PubMed: 17609377
DOI: 10.1073/pnas.0704057104

実験手法

SOLUTION NMR