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

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.
Authors:
 [1] ;  [1] ;  [1] ;  [2] ; ORCiD logo [3]
  1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics. Dept. of Biochemistry
  2. 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
  3. 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
Publication Date:
OSTI Identifier:
1214045
Grant/Contract Number:
AC02-06CH11357; R01 GM081875; R01 GM106239; I-1424
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 111; Journal Issue: 50; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
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 Org:
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 Orgs:
City College of New York, NY (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; two-component system; cell signaling; histidine kinase; photosensory; regulation