Elucidating the signal transduction mechanism of the blue-light-regulated photoreceptor YtvA: From photoactivation to downstream regulation

He, YongLe, Collado, Jinnette Tolentino, Iuliano, James N., Woroniecka, Helena A., Hall, Christopher R., Gil, Agnieszka A., Laptenok, Sergey P., Greetham, Gregory M., Illarionov, Boris, Bacher, Adelbert, Fischer, Markus, French, Jarrod B., Lukacs, Andras, Meech, Stephen R. ORCID: https://orcid.org/0000-0001-5561-2782 and Tonge, Peter J. (2024) Elucidating the signal transduction mechanism of the blue-light-regulated photoreceptor YtvA: From photoactivation to downstream regulation. ACS Chemical Biology, 19 (3). pp. 696-706. ISSN 1554-8929

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The blue-light photoreceptor YtvA from Bacillus subtilis has an N-terminal flavin mononucleotide (FMN)-binding light-oxygen-voltage (LOV) domain that is fused to a C-terminal sulfate transporter and anti-σ factor antagonist (STAS) output domain. To interrogate the signal transduction pathway that leads to photoactivation, the STAS domain was replaced with a histidine kinase, so that photoexcitation of the flavin could be directly correlated with biological activity. N94, a conserved Asn that is hydrogen bonded to the FMN C2═O group, was replaced with Ala, Asp, and Ser residues to explore the role of this residue in triggering the structural dynamics that activate the output domain. Femtosecond to millisecond time-resolved multiple probe spectroscopy coupled with a fluorescence polarization assay revealed that the loss of the hydrogen bond between N94 and the C2═O group decoupled changes in the protein structure from photoexcitation. In addition, alterations in N94 also decreased the stability of the Cys-FMN adduct formed in the light-activated state by up to a factor of ∼25. Collectively, these studies shed light on the role of the hydrogen bonding network in the LOV β-scaffold in signal transduction.

Item Type: Article
Additional Information: Funding Information: J.T.C. was supported by the National Institutes of Health IMSD-MERGE (T32GM135746) and NY-CAPs IRACDA (K12-GM102778) Programs at Stony Brook University. A.L. acknowledges funding from the Hungarian National Research and Innovation Office (K-137557) and was supported by PTE ÁOK-KA-2021. This study was supported by the National Science Foundation (NSF) (MCB-1817837 to P.J.T.) and the EPSRC (EP/N033647/1 to S.R.M.). Y.H. and J.N.I were supported by a National Institutes of Health Chemistry-Biology Interface Training Grant (T32GM092714). The authors are grateful to STFC for access to the ULTRA laser facility.
Faculty \ School: Faculty of Science > School of Chemistry
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Depositing User: LivePure Connector
Date Deposited: 30 May 2024 15:30
Last Modified: 05 Jun 2024 11:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/95343
DOI: 10.1021/acschembio.3c00722


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