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

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

Departments of ^*Biochemistry and ^§Chemistry and the ^†Plant Biotechnology Center, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210

Communicated by Max F. Perutz, Medical Research Council, Cambridge, United Kingdom (received for review October 2, 1998)

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.

Footnotes

↵ ¶ To whom reprint requests should be addressed. e-mail: chan{at}chemistry.ohio-state.edu.
↵ ‡ To whom reprint requests should be addressed at Plant Biotechnology Center, The Ohio State University, 1060 Carmack Road, Columbus, OH 43210-1002. e-mail: gilles-gonzalez.1{at}osu.edu.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, Biology Department, Brookhaven National Laboratory, Upton, NY 11973 [PDB ID codes 1BV6 (met-BjFixLH) and 1BV5 (cyanomet-BjFixLH)].
ABBREVIATIONS:

BjFixLH,

Bradyrhizobium japonicum FixL heme domain;

MAD,

multiwavelength anomalous diffraction;

PAS,

an acronym formed from the names of the first proteins recognized as sharing this sensory motif, i.e., the period clock protein of Drosophila, the aryl hydrocarbon receptor nuclear translocator of vertebrates, and the single-minded protein of Drosophila;

PYP,

photoactive yellow protein