A hyperpromiscuous antitoxin protein domain for the neutralization of diverse toxin domains-Reference-Cited by-同舟云学术

A hyperpromiscuous antitoxin protein domain for the neutralization of diverse toxin domains

Published:2022-02-04 Issue:6 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Kurata Tatsuaki¹,Saha Chayan Kumar¹²^ORCID,Buttress Jessica A.³^ORCID,Mets Toomas⁴^ORCID,Brodiazhenko Tetiana⁴,Turnbull Kathryn J.⁵,Awoyomi Ololade F.⁶^ORCID,Oliveira Sofia Raquel Alves⁴^ORCID,Jimmy Steffi⁷,Ernits Karin⁸^ORCID,Delannoy Maxence⁹,Persson Karina⁸^ORCID,Tenson Tanel⁴^ORCID,Strahl Henrik³^ORCID,Hauryliuk Vasili¹²⁴¹⁰^ORCID,Atkinson Gemma C.¹²^ORCID

Affiliation:

1. Department of Experimental Medicine, University of Lund, 221 84 Lund, Sweden

2. Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden

3. Center for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom

4. University of Tartu, Institute of Technology, 50411 Tartu, Estonia

5. Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen, Denmark

6. Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden

7. Center for Structural Systems Biology, Deutsches Elektronen-Synchrotron, 22607 Hamburg, Germany

8. Department of Chemistry, Umeå University, 901 87 Umeå, Sweden

9. Département Génie Biologique, Campus SophiaTech, Université Nice Sophia Antipolis, 06000 Nice, France

10. Laboratory for Molecular Infection Medicine Sweden, Umeå University, 901 87 Umeå, Sweden

Abstract

Significance Toxin–antitoxin systems are enigmatic and diverse elements of bacterial and bacteriophage genomes. We have uncovered remarkable versatility in an antitoxin protein domain that has evolved to neutralize dozens of different toxin domains. We find that antitoxins carrying this domain—Panacea—form complexes with their cognate toxins, indicating a direct neutralization mechanism, and that Panacea can be evolved to neutralize a noncognate and nonhomologous toxin with just two amino acid substitutions. This raises the possibility that this domain could be an adaptable universal or semi-universal protein neutralizer with significant biotechnological and medical potential.

Funder

Knut och Alice Wallenbergs Stiftelse

Vetenskapsrådet

Ragnar Soderbergs Stiftelse

Umeå Centre for Microbial Research

Kempestiftelserna

Carl Tryggers Stiftelse för Vetenskaplig Forskning

Umeå University Medical Faculty

European Union from the European Regional Development Fund through the Centre of Excellence in Molecular Cell Engineering

Estonian Research Council

RCUK | Biotechnology and Biological Sciences Research Council

RCUK | Medical Research Council