5JHQ

ARCs 1-3 of human Tankyrase-1 bound to a peptide derived from IRAP

Summary for 5JHQ

• Entry DOI: 10.2210/pdb5jhq/pdb
• Descriptor: Tankyrase-1, Peptide derived from insulin-responsive aminopeptidase (IRAP) (3 entities in total)
• Functional Keywords: adp-ribosyl transferase, parp, transferase, tankyrase-1, tnks
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 221255.36

Authors

Eisemann, T.,Pascal, J.M. (deposition date: 2016-04-21, release date: 2016-09-21, Last modification date: 2024-10-23)

Primary citation

Eisemann, T.,McCauley, M.,Langelier, M.F.,Gupta, K.,Roy, S.,Van Duyne, G.D.,Pascal, J.M.
Tankyrase-1 Ankyrin Repeats Form an Adaptable Binding Platform for Targets of ADP-Ribose Modification.
Structure, 24:1679-1692, 2016

PubMed Abstract: The poly(ADP-ribose) polymerase enzyme Tankyrase-1 (TNKS) regulates multiple cellular processes and interacts with diverse proteins using five ankyrin repeat clusters (ARCs). There are limited structural insights into functional roles of the multiple ARCs of TNKS. Here we present the ARC1-3 crystal structure and employ small-angle X-ray scattering (SAXS) to investigate solution conformations of the complete ankyrin repeat domain. Mutagenesis and binding studies using the bivalent TNKS binding domain of Axin1 demonstrate that only certain ARC combinations function together. The physical basis for these restrictions is explained by both rigid and flexible ankyrin repeat elements determined in our structural analysis. SAXS analysis is consistent with a dynamic ensemble of TNKS ankyrin repeat conformations modulated by Axin1 interaction. TNKS ankyrin repeat domain is thus an adaptable binding platform with structural features that can explain selectivity toward diverse proteins, and has implications for TNKS positioning of bound targets for poly(ADP-ribose) modification.

PubMed: 27594684
DOI: 10.1016/j.str.2016.07.014

Experimental method

X-RAY DIFFRACTION (3.2 Å)