5JTI

Crystal structure of the human Tankyrase 1 (TNKS) SAM domain (D1055R), crystal form 2

5JTI の概要

• エントリーDOI: 10.2210/pdb5jti/pdb
• 分子名称: Tankyrase-1 (2 entities in total)
• 機能のキーワード: tankyrase polymerisation wnt signalling poly(adp-ribose)polymerase (parp), transferase, signaling protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: O95271
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 53124.35

構造登録者

Guetter, S.,Mariotti, L.,Cronin, N. (登録日: 2016-05-09, 公開日: 2016-08-03, 最終更新日: 2024-01-10)

主引用文献

Mariotti, L.,Templeton, C.M.,Ranes, M.,Paracuellos, P.,Cronin, N.,Beuron, F.,Morris, E.,Guettler, S.
Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-beta-Catenin Signaling.
Mol.Cell, 63:498-513, 2016

PubMed Abstract: The poly(ADP-ribose) polymerase (PARP) Tankyrase (TNKS and TNKS2) is paramount to Wnt-β-catenin signaling and a promising therapeutic target in Wnt-dependent cancers. The pool of active β-catenin is normally limited by destruction complexes, whose assembly depends on the polymeric master scaffolding protein AXIN. Tankyrase, which poly(ADP-ribosyl)ates and thereby destabilizes AXIN, also can polymerize, but the relevance of these polymers has remained unclear. We report crystal structures of the polymerizing TNKS and TNKS2 sterile alpha motif (SAM) domains, revealing versatile head-to-tail interactions. Biochemical studies informed by these structures demonstrate that polymerization is required for Tankyrase to drive β-catenin-dependent transcription. We show that the polymeric state supports PARP activity and allows Tankyrase to effectively access destruction complexes through enabling avidity-dependent AXIN binding. This study provides an example for regulated signal transduction in non-membrane-enclosed compartments (signalosomes), and it points to novel potential strategies to inhibit Tankyrase function in oncogenic Wnt signaling.

PubMed: 27494558
DOI: 10.1016/j.molcel.2016.06.019

実験手法

X-RAY DIFFRACTION (2.9 Å)