3TWX

Crystal structure of ARC4 from human Tankyrase 2 in complex with peptide from human FNBP1 (chimeric peptide)

3TWX の概要

• エントリーDOI: 10.2210/pdb3twx/pdb
• 関連するPDBエントリー: 3TWQ 3TWR 3TWS 3TWT 3TWU 3TWV 3TWW
• 分子名称: Tankyrase-2, human FNBP1, HEXAETHYLENE GLYCOL, ... (6 entities in total)
• 機能のキーワード: ankyrin repeat, protein-protein interaction, substrate recruitment, poly(adp-ribosyl)ation, signaling protein-peptide complex, signaling protein/peptide
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q9H2K2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 40301.20

構造登録者

Guettler, S.,Sicheri, F. (登録日: 2011-09-22, 公開日: 2011-12-07, 最終更新日: 2025-03-26)

主引用文献

Guettler, S.,Larose, J.,Petsalaki, E.,Gish, G.,Scotter, A.,Pawson, T.,Rottapel, R.,Sicheri, F.
Structural basis and sequence rules for substrate recognition by tankyrase explain the basis for cherubism disease.
Cell(Cambridge,Mass.), 147:1340-1354, 2011

PubMed Abstract: The poly(ADP-ribose)polymerases Tankyrase 1/2 (TNKS/TNKS2) catalyze the covalent linkage of ADP-ribose polymer chains onto target proteins, regulating their ubiquitylation, stability, and function. Dysregulation of substrate recognition by Tankyrases underlies the human disease cherubism. Tankyrases recruit specific motifs (often called RxxPDG "hexapeptides") in their substrates via an N-terminal region of ankyrin repeats. These ankyrin repeats form five domains termed ankyrin repeat clusters (ARCs), each predicted to bind substrate. Here we report crystal structures of a representative ARC of TNKS2 bound to targeting peptides from six substrates. Using a solution-based peptide library screen, we derive a rule-based consensus for Tankyrase substrates common to four functionally conserved ARCs. This 8-residue consensus allows us to rationalize all known Tankyrase substrates and explains the basis for cherubism-causing mutations in the Tankyrase substrate 3BP2. Structural and sequence information allows us to also predict and validate other Tankyrase targets, including Disc1, Striatin, Fat4, RAD54, BCR, and MERIT40.

PubMed: 22153077
DOI: 10.1016/j.cell.2011.10.046

実験手法

X-RAY DIFFRACTION (1.8 Å)