The bacteriophage-phage-inducible chromosomal island arms race designs an interkingdom inhibitor of dUTPases
Author(s)
Sanz-Frasquet, Carla
Rafael Ciges-Tomas, J
Alite, Christian
Penades, Jose R
Marina, Alberto
Type
Journal Article
Abstract
Stl, the master repressor of the Staphylococcus aureus pathogenicity islands (SaPIs), targets phage-encoded proteins to derepress and synchronize the SaPI and the helper phage life cycles. To activate their cycle, some SaPI Stls target both phage dimeric and phage trimeric dUTPases (Duts) as antirepressors, which are structurally unrelated proteins that perform identical functions for the phage. This intimate link between the SaPI’s repressor and the phage inducer has imposed an evolutionary optimization of Stl that allows the interaction with Duts from unrelated organisms. In this work, we structurally characterize this sophisticated mechanism of specialization by solving the structure of the prototypical SaPIbov1 Stl in complex with a prokaryotic and a eukaryotic trimeric Dut. The heterocomplexes with Mycobacterium tuberculosis and Homo sapiens Duts show the molecular strategy of Stl to target trimeric Duts from different kingdoms. Our structural results confirm the participation of the five catalytic motifs of trimeric Duts in Stl binding, including the C-terminal flexible motif V that increases the affinity by embracing Stl. In silico and in vitro analyses with a monomeric Dut support the capacity of Stl to recognize this third family of Duts, confirming this protein as a universal Dut inhibitor in the different kingdoms of life.
Date Issued
2023-02-14
Date Acceptance
2022-12-18
Citation
Microbiology Spectrum, 2023, 11 (1)
ISSN
2165-0497
Publisher
American Society for Microbiology
Journal / Book Title
Microbiology Spectrum
Volume
11
Issue
1
Copyright Statement
© 2023 Sanz-Frasquet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000910546000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
ASSAY
crystal structure
DNA
dUTPase
Dut-Stl complex
GENES
inhibition
Life Sciences & Biomedicine
MECHANISM
Microbiology
PICI
protein-protein interaction
REPRESSOR
Science & Technology
SEQUENCE ALIGNMENT
STAPHYLOCOCCUS-AUREUS
Stl repressor
TOOL
URACIL
Publication Status
Published
Article Number
e03232-22
Date Publish Online
2023-01-09