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. https://doi.org/10.1098/rsob.210365
The zinc-binding motif in tankyrases is required for the structural integrity of the catalytic ADP-ribosyltransferase domain
|Author:||Sowa, Sven T.1; Lehtiö, Lari1|
1Faculty for Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 1.4 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022121671992
The Royal Society,
|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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
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 (Academy of Finland Funding decision)
294085 (Academy of Finland Funding decision)
319299 (Academy of Finland Funding decision)
© 2022 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.