Crystal structure and function of the zinc uptake regulator FurB from Mycobacterium tuberculosis.
Members of the ferric/zinc uptake regulator (Fur/Zur) family are the central metal-dependent regulator proteins in many Gram-negative and -positive bacteria. They are responsible for the control of a wide variety of basic physiological processes and the expression of important virulence factors in human pathogens. Therefore, Fur has gathered significant interest as a potential target for novel antibiotics. Here we report the crystal structure of FurB from Mycobacterium tuberculosis at a resolution of 2.7A, and we present biochemical and spectroscopic data that allow us to propose the functional role of this protein. Although the overall fold of FurB with an N-terminal DNA binding domain and a C-terminal dimerization domain is conserved among the Zur/Fur family, large differences in the spatial arrangement of the two domains with respect to each other can be observed. The biochemical and spectroscopic analysis presented here reveals that M. tuberculosis FurB is Zn(II)-dependent and is likely to control genes involved in the bacterial zinc uptake. The combination of the structural, spectroscopic, and biochemical results enables us to determine the structural basis for functional differences in this important family of bacterial regulators.
Lucarelli
Debora
D
European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany.
Russo
Santina
S
Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen, Switzerland.
Garman
Elspeth
E
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
Milano
Anna
A
Department of Genetics and Microbiology, University of Pavia, 27100 Pavia, Italy.
Meyer-Klaucke
Wolfram
W
European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany. Electronic address: wolfram@embl-hamburg.de.
Pohl
Ehmke
E
Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen, Switzerland. Electronic address: ehmke.pohl@psi.ch.
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D015032:Zinc