The N-terminal FleQ domain of the Vibrio cholerae flagellar master regulator FlrA plays pivotal structural roles in stabilizing its active state.

Autor: Chakraborty S; Department of Biotechnology, St Xavier's College, Kolkata, India., Agarwal S; Department of Biotechnology, St Xavier's College, Kolkata, India., Bakshi A; Department of Biotechnology, St Xavier's College, Kolkata, India., Dey S; Department of Biotechnology, St Xavier's College, Kolkata, India., Biswas M; Department of Biotechnology, St Xavier's College, Kolkata, India., Ghosh B; Beamline Development and Application Section, Bhabha Atomic Research Centre, Mumbai, India., Dasgupta J; Department of Biotechnology, St Xavier's College, Kolkata, India.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2023 Sep; Vol. 597 (17), pp. 2161-2177. Date of Electronic Publication: 2023 Jul 10.
DOI: 10.1002/1873-3468.14693
Abstrakt: In Vibrio cholerae, the master regulator FlrA controls transcription of downstream flagellar genes in a σ 54 -dependent manner. However, the molecular basis of regulation by VcFlrA, which contains a phosphorylation-deficient N-terminal FleQ domain, has remained elusive. Our studies on VcFlrA, four of its constructs, and a mutant showed that the AAA + domain of VcFlrA, with or without the linker 'L', remains in ATPase-deficient monomeric states. By contrast, the FleQ domain plays a pivotal role in promoting higher-order functional oligomers, providing the required conformation to 'L' for ATP/cyclic di-GMP (c-di-GMP) binding. The crystal structure of VcFlrA-FleQ at 2.0 Å suggests that distinct structural features of VcFlrA-FleQ presumably assist in inter-domain packing. VcFlrA at a high concentration forms ATPase-efficient oligomers when the intracellular c-di-GMP level is low. Conversely, excess c-di-GMP locks VcFlrA in a non-functional lower oligomeric state, causing repression of flagellar biosynthesis.
(© 2023 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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