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PMID: 9860942 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Structure of a biological oxygen sensor: a new mechanism for heme-driven signal transduction.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 26 ·1998-12-22 ·Pages 15177-82

Gong W, Hao B, Mansy SS, Gonzalez G, Gilles-Gonzalez MA, Chan MK

Abstract

The FixL proteins are biological oxygen sensors that restrict the expression of specific genes to hypoxic conditions. FixL's oxygen-detecting domain is a heme binding region that controls the activity of an attached histidine kinase. The FixL switch is regulated by binding of oxygen and other strong-field ligands. In the absence of bound ligand, the heme domain permits kinase activity. In the presence of bound ligand, this domain turns off kinase activity. Comparison of the structures of two forms of the Bradyrhizobium japonicum FixL heme domain, one in the "on" state without bound ligand and one in the "off" state with bound cyanide, reveals a mechanism of regulation by a heme that is distinct from the classical hemoglobin models. The close structural resemblance of the FixL heme domain to the photoactive yellow protein confirms the existence of a PAS structural motif but reveals the presence of an alternative regulatory gateway.

MeSH Terms
Amino Acid Sequence Animals Bacterial Proteins/chemistry,genetics,metabolism Binding Sites Biosensing Techniques Bradyrhizobium/genetics,metabolism Crystallography, X-Ray Heme/chemistry,metabolism Hemeproteins/chemistry,genetics,metabolism Histidine Kinase Kinetics Ligands Models, Molecular Molecular Sequence Data Myoglobin/chemistry,metabolism Oxygen/metabolism Protein Kinases/chemistry,genetics,metabolism Protein Structure, Secondary Sequence Alignment Sequence Homology, Amino Acid Signal Transduction Whales
Chemicals
Bacterial Proteins Hemeproteins Ligands Myoglobin Heme Protein Kinases FixL protein, Bacteria Histidine Kinase Oxygen
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gong W
Department of Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA.
Hao B
Mansy S S
Gonzalez G
Gilles-Gonzalez M A
Chan M K
References (36)
36 references, click to expand
  1. Communication modules in bacterial signaling proteins.
    Annu Rev Genet. 1992;26:71-112 PMID: 1482126
  2. Raster3D Version 2.0. A program for photorealistic molecular graphics.
    Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):869-73 PMID: 15299354
  3. Assessment of phase accuracy by cross validation: the free R value. Methods and applications.
    Acta Crystallogr D Biol Crystallogr. 1993 Jan 1;49(Pt 1):24-36 PMID: 15299543
  4. The FixL protein of Rhizobium meliloti can be separated into a heme-binding oxygen-sensing domain and a functional C-terminal kinase domain.
    Proc Natl Acad Sci U S A. 1992 May 15;89(10):4280-4 PMID: 1584762
  5. The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development.
    Cell. 1991 Dec 20;67(6):1157-67 PMID: 1760843
  6. A haemoprotein with kinase activity encoded by the oxygen sensor of Rhizobium meliloti.
    Nature. 1991 Mar 14;350(6314):170-2 PMID: 1848683
  7. PHASES-95: a program package for processing and analyzing diffraction data from macromolecules.
    Methods Enzymol. 1997;277:590-620 PMID: 18488326
  8. The regulatory status of the fixL- and fixJ-like genes in Bradyrhizobium japonicum may be different from that in Rhizobium meliloti.
    Mol Gen Genet. 1991 Jan;225(1):38-48 PMID: 2000090
  9. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  10. Glycera dibranchiata hemoglobin. Structure and refinement at 1.5 A resolution.
    J Mol Biol. 1989 Nov 5;210(1):149-61 PMID: 2585515
  11. Mechanisms of cooperativity and allosteric regulation in proteins.
    Q Rev Biophys. 1989 May;22(2):139-237 PMID: 2675171
  12. Processing of X-ray diffraction data collected in oscillation mode.
    Methods Enzymol. 1997;276:307-26 PMID: 27754618
  13. Cascade regulation of nif gene expression in Rhizobium meliloti.
    Cell. 1988 Aug 26;54(5):671-83 PMID: 2842062
  14. Crystallographic refinement by simulated annealing. Application to a 2.8 A resolution structure of aspartate aminotransferase.
    J Mol Biol. 1988 Oct 5;203(3):803-16 PMID: 3062181
  15. Characterization of a second gene involved in bacterio-opsin gene expression in a halophilic archaebacterium.
    J Bacteriol. 1988 Oct;170(10):4903-9 PMID: 3170488
  16. Stereochemistry of cooperative effects in haemoglobin.
    Nature. 1970 Nov 21;228(5273):726-39 PMID: 5528785
  17. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features.
    Biopolymers. 1983 Dec;22(12):2577-637 PMID: 6667333
  18. Kinase activity of oxygen sensor FixL depends on the spin state of its heme iron.
    Biochemistry. 1995 Jan 10;34(1):232-6 PMID: 7819201
  19. Guanylyl cyclase receptors.
    J Biol Chem. 1994 Dec 9;269(49):30741-4 PMID: 7982997
  20. Heme-based sensors, exemplified by the kinase FixL, are a new class of heme protein with distinctive ligand binding and autoxidation.
    Biochemistry. 1994 Jul 5;33(26):8067-73 PMID: 8025112
  21. Oxygen-regulated in vitro transcription of Rhizobium meliloti nifA and fixK genes.
    J Bacteriol. 1993 Nov;175(21):6867-72 PMID: 8226629
  22. High-resolution crystal structures of distal histidine mutants of sperm whale myoglobin.
    J Mol Biol. 1993 Nov 5;234(1):140-55 PMID: 8230194
  23. Sequence and molecular analysis of the nifL gene of Azotobacter vinelandii.
    Mol Microbiol. 1993 Aug;9(4):869-79 PMID: 8231815
  24. Regulation of the kinase activity of heme protein FixL from the two-component system FixL/FixJ of Rhizobium meliloti.
    J Biol Chem. 1993 Aug 5;268(22):16293-7 PMID: 8393856
  25. Oxygen regulation of nifA transcription in vitro.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3506-10 PMID: 8475099
  26. Mechanism of NO-induced oxidation of myoglobin and hemoglobin.
    Biochemistry. 1996 Jun 4;35(22):6976-83 PMID: 8679521
  27. Azotobacter vinelandii NIFL is a flavoprotein that modulates transcriptional activation of nitrogen-fixation genes via a redox-sensitive switch.
    Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2143-8 PMID: 8700899
  28. Structural basis for ligand discrimination and response initiation in the heme-based oxygen sensor FixL.
    Biochemistry. 1996 Jul 23;35(29):9539-48 PMID: 8755735
  29. Assignment of the hyperfine-shifted 1H-NMR signals of the heme in the oxygen sensor FixL from Rhizobium meliloti.
    Chem Biol. 1996 Jul;3(7):561-6 PMID: 8807888
  30. Nonsteric factors dominate binding of nitric oxide, azide, imidazole, cyanide, and fluoride to the rhizobial heme-based oxygen sensor FixL.
    Chem Biol. 1996 Oct;3(10):841-50 PMID: 8939703
  31. Structure of a protein photocycle intermediate by millisecond time-resolved crystallography.
    Science. 1997 Mar 7;275(5305):1471-5 PMID: 9045611
  32. PAS domain S-boxes in Archaea, Bacteria and sensors for oxygen and redox.
    Trends Biochem Sci. 1997 Sep;22(9):331-3 PMID: 9301332
  33. CooA, a CO-sensing transcription factor from Rhodospirillum rubrum, is a CO-binding heme protein.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11216-20 PMID: 9326589
  34. Crystal structures of a nitric oxide transport protein from a blood-sucking insect.
    Nat Struct Biol. 1998 Apr;5(4):304-9 PMID: 9546222
  35. Photoactive yellow protein: a structural prototype for the three-dimensional fold of the PAS domain superfamily.
    Proc Natl Acad Sci U S A. 1998 May 26;95(11):5884-90 PMID: 9600888
  36. Imidazole is a sensitive probe of steric hindrance in the distal pockets of oxygen-binding heme proteins.
    Biochemistry. 1998 Sep 8;37(36):12452-7 PMID: 9730817
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.26.15177
Published
1998-12-22
Pages
15177-82
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC28016
Subset
IM
Grants
NIAID NIH HHS · R01 AI040575 · United States
NIAID NIH HHS · AI-40575-02 · United States
Databases
PDB
1BV5, 1BV6
External Links
PubMed source DOI: 10.1073/pnas.95.26.15177 PMC Full Text View journal details
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