University of Oulu

Sowa ST, Lehtiö L. 2022 Thezinc-binding motif in tankyrases is required forthe structural integrity of the catalytic ADP-ribosyltransferase domain.Open Biol.12:210365.

The zinc-binding motif in tankyrases is required for the structural integrity of the catalytic ADP-ribosyltransferase domain

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Author: Sowa, Sven T.1; Lehtiö, Lari1
Organizations: 1Faculty for Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: The Royal Society, 2022
Publish Date: 2022-12-16


Tankyrases are ADP-ribosylating enzymes that regulate many physiological processes in the cell and are considered promising drug targets for cancer and fibrotic diseases. The catalytic ADP-ribosyltransferase domain of tankyrases contains a unique zinc-binding motif of unknown function. Recently, this motif was suggested to be involved in the catalytic activity of tankyrases. In this work, we set out to study the effect of the zinc-binding motif on the activity, stability and structure of human tankyrases. We generated mutants of human tankyrase (TNKS) 1 and TNKS2, abolishing the zinc-binding capabilities, and characterized the proteins biochemically and biophysically in vitro. We further generated a crystal structure of TNKS2, in which the zinc ion was oxidatively removed. Our work shows that the zinc-binding motif in tankyrases is a crucial structural element which is particularly important for the structural integrity of the acceptor site. While mutation of the motif rendered TNKS1 inactive, probably due to introduction of major structural defects, the TNKS2 mutant remained active and displayed an altered activity profile compared to the wild-type.

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Series: Open biology
ISSN: 2046-2441
ISSN-E: 2046-2441
ISSN-L: 2046-2441
Volume: 12
Issue: 3
Article number: 210365
DOI: 10.1098/rsob.210365
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: The work was funded by the Jane and Aatos Erkko Foundation and the Academy of Finland (grant nos. 287063, 294085 and 319299).
Academy of Finland Grant Number: 287063
Detailed Information: 287063 (Academy of Finland Funding decision)
294085 (Academy of Finland Funding decision)
319299 (Academy of Finland Funding decision)
Copyright information: © 2022 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited.