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Photoactivation Mechanism of a Bacterial Light-Regulated Adenylyl Cyclase

Lindner, Robert and Hartmann, Elisabeth and Tarnawski, Miroslaw and Winkler, Andreas and Lenherr-Frey, Daniel and Reinstein, Jochen and Meinhart, Anton and Schlichting, Ilme (2017) Photoactivation Mechanism of a Bacterial Light-Regulated Adenylyl Cyclase. Journal of Molecular Biology, 429 (9). pp. 1336-1351. ISSN 00222836

Abstract

Light-regulated enzymes enable organisms to quickly respond to changing light conditions. We characterize a photoactivatable adenylyl cyclase (AC) from Beggiatoa sp. (bPAC) that translates a blue light signal into the production of the secondmessenger cyclicAMP. bPACcontains a BLUF photoreceptor domain that senses blue light using a flavin chromophore, linked to an AC domain. We present a dark state crystal structure of bPAC that closely resembles the recently published structure of the homologous OaPAC from Oscillatoria acuminata. To elucidate the structural mechanism of light-dependent AC activation by the BLUF domain, we determined the crystal structures of illuminated bPAC and of a pseudo-lit state variant. We use hydrogen– deuteriumexchangemeasurements of secondary structure dynamics and hypothesis-driven point mutations to trace the activation pathway from the chromophore in the BLUF domain to the active site of the cyclase. The structural changes are relayed fromthe residues interacting with the excited chromophore through a conserved kink of the BLUF β-sheet to a tongue-like extrusion of the AC domain that regulates active site opening and repositions catalytic residues. Our findings not only show the specific molecular pathway of photoactivation in BLUF-regulatedACs but also have implications for the general understanding of signaling in BLUFdomains and of the activation of ACs.

Item Type: Article
Date Deposited: 27 Apr 2017 00:45
Last Modified: 27 Apr 2017 00:45
URI: https://oak.novartis.com/id/eprint/32901

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