Control of biofilm formation by an Agrobacterium tumefaciens pterin-binding periplasmic protein conserved among diverse Proteobacteria .

Autor:	Greenwich JL; Department of Biology, Indiana University, Bloomington, IN 47405., Eagan JL; Department of Biology, Indiana University, Bloomington, IN 47405., Feirer N; Department of Biology, Indiana University, Bloomington, IN 47405., Boswinkle K; Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061., Minasov G; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.; Center for Structural Biology of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611., Shuvalova L; Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611., Inniss NL; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.; Center for Structural Biology of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611., Raghavaiah J; Department of Chemistry, Purdue University, West Lafayette, IN 47907.; Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907., Ghosh AK; Department of Chemistry, Purdue University, West Lafayette, IN 47907.; Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907., Satchell KJF; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.; Center for Structural Biology of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611., Allen KD; Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061., Fuqua C; Department of Biology, Indiana University, Bloomington, IN 47405.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jun 18; Vol. 121 (25), pp. e2319903121. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1073/pnas.2319903121
Abstrakt:	Biofilm formation and surface attachment in multiple Alphaproteobacteria is driven by unipolar polysaccharide (UPP) adhesins. The pathogen Agrobacterium tumefaciens produces a UPP adhesin, which is regulated by the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP). Prior studies revealed that DcpA, a diguanylate cyclase-phosphodiesterase, is crucial in control of UPP production and surface attachment. DcpA is regulated by PruR, a protein with distant similarity to enzymatic domains known to coordinate the molybdopterin cofactor (MoCo). Pterins are bicyclic nitrogen-rich compounds, several of which are produced via a nonessential branch of the folate biosynthesis pathway, distinct from MoCo. The pterin-binding protein PruR controls DcpA activity, fostering c-di-GMP breakdown and dampening its synthesis. Pterins are excreted, and we report here that PruR associates with these metabolites in the periplasm, promoting interaction with the DcpA periplasmic domain. The pteridine reductase PruA, which reduces specific dihydro-pterin molecules to their tetrahydro forms, imparts control over DcpA activity through PruR. Tetrahydromonapterin preferentially associates with PruR relative to other related pterins, and the PruR-DcpA interaction is decreased in a pruA mutant. PruR and DcpA are encoded in an operon with wide conservation among diverse Proteobacteria including mammalian pathogens. Crystal structures reveal that PruR and several orthologs adopt a conserved fold, with a pterin-specific binding cleft that coordinates the bicyclic pterin ring. These findings define a pterin-responsive regulatory mechanism that controls biofilm formation and related c-di-GMP-dependent phenotypes in A. tumefaciens and potentially acts more widely in multiple proteobacterial lineages. Competing Interests: Competing interests statement:K.J.F.S. has a significant interest in Situ Biosciences, a contract research organization that conducts research unrelated to this study. K.J.F.S. and her spouse are 100% owners of Situ Biosciences. All other authors declare no conflicts of interest.
Databáze:	MEDLINE
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