3TWU: Crystal Structure Of Arc4 From Human Tankyrase 2 In Complex With Peptide From Human Mcl1

Citation:
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.
PDB ID: 3TWUDownload
MMDB ID: 95574
PDB Deposition Date: 2011/9/22
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3TWU: dimeric; determined by software (PISA)
Molecular Components in 3TWU
Label Count Molecule
Proteins (2 molecules)
1
Tankyrase-2(Gene symbol: TNKS2)
Molecule annotation
1
Induced Myeloid Leukemia Cell Differentiation Protein Mcl- 1(Gene symbol: MCL1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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