5JU5: Crystal Structure Of The Human Tankyrase 1 (tnks) Sam Domain (d1055r), Crystal Form 1

Citation:
Abstract
The poly(ADP-ribose) polymerase (PARP) Tankyrase (TNKS and TNKS2) is paramount to Wnt-beta-catenin signaling and a promising therapeutic target in Wnt-dependent cancers. The pool of active beta-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 beta-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.
PDB ID: 5JU5Download
MMDB ID: 141573
PDB Deposition Date: 2016/5/10
Updated in MMDB: 2016/10
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 5JU5: hexameric; determined by author and by software (PISA)
Molecular Components in 5JU5
Label Count Molecule
Proteins (6 molecules)
6
Tankyrase-1(Gene symbol: TNKS)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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