Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase

The ability to respond to light is crucial for most organisms. BLUF is a recently identified photoreceptor protein domain that senses blue light using a FAD chromophore. BLUF domains are present in various proteins from the Bacteria, Euglenozoa and Fungi. Although structures of single-domain BLUF proteins have been determined, none are available for a BLUF protein containing a functional output domain; the mechanism of light activation in this new class of photoreceptors has thus remained poorly understood. Here we report the biochemical, structural and mechanistic characterization of a full-length, active photoreceptor, BlrP1 (also known as KPN_01598), from Klebsiella pneumoniae. BlrP1 consists of a BLUF sensor domain and a phosphodiesterase EAL output domain which hydrolyses cyclic dimeric GMP (c-di-GMP). This ubiquitous second messenger controls motility, biofilm formation, virulence and antibiotic resistance in the Bacteria. Crystal structures of BlrP1 complexed with its substrate and metal ions involved in catalysis or in enzyme inhibition provide a detailed understanding of the mechanism of the EAL-domain c-di-GMP phosphodiesterases. These structures also sketch out a path of light activation of the phosphodiesterase output activity. Photon absorption by the BLUF domain of one subunit of the antiparallel BlrP1 homodimer activates the EAL domain of the second subunit through allosteric communication transmitted through conserved domain-domain interfaces.

Ingår i:Nature: Springer Science and Business Media LLC459, s. 1015-10180028-08361476-4687

Av författaren/redakt...: Barends, Thomas ...; Hartmann, Elisab ...; Griese, Julia J.; Beitlich, Thorst ...; Kirienko, Natali ...; Ryjenkov, Dmitri ...; visa fler...; Reinstein, Joche ...; Shoeman, Robert ...; Gomelsky, Mark; Schlichting, Ilm ...; visa färre...

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