Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation

Rivera-Cancel, Giomar; Ko, Wen-huang; Tomchick, Diana R.; Correa, Fernando; Gardner, Kevin H.

doi:10.1073/pnas.1413983111

Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation

Journal Article · Tue Dec 02 04:00:00 EST 2014 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1413983111· OSTI ID:1214045

Rivera-Cancel, Giomar ^[1]; Ko, Wen-huang ^[1]; Tomchick, Diana R. ^[1]; Correa, Fernando ^[2]; ^[3]

Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics. Dept. of Biochemistry
Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics. Dept. of Biochemistry; City Univ. of New York Advanced Science Research Center, New York, NY (United States). Structural Biology Initiative
Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics. Dept. of Biochemistry; City Univ. of New York Advanced Science Research Center, New York, NY (United States). Structural Biology Initiative; City College of New York, NY (United States). Dept. of Chemistry

Although histidine kinases (HKs) are critical sensors of external stimuli in prokaryotes, the mechanisms by which their sensor domains control enzymatic activity remain unclear. In this paper, we report the full-length structure of a blue light-activated HK from Erythrobacter litoralis HTCC2594 (EL346) and the results of biochemical and biophysical studies that explain how it is activated by light. Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer. Its structure reveals that the light–oxygen–voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain. The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark. Upon light stimulation, interdomain interactions weaken to facilitate activation. Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation. Finally, we suggest parallels between EL346 and dimeric HKs, with sensor-induced movements in the DHp similarly remodeling the DHp/CA interface as part of activation.

View Accepted Manuscript (DOE)

Research Organization:: City Univ. of New York Advanced Science Research Center, New York, NY (United States); Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH) (United States); Robert A. Welch Foundation (United States)

Contributing Organization:: City College of New York, NY (United States)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1214045

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 50 Vol. 111; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
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Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation

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