The structure of a full-length response regulator from Mycobacterium tuberculosis in a stabilized three-dimensional domain-swapped, activated state.
The full-length, two-domain response regulator RegX3 from Mycobacterium tuberculosis is a dimer stabilized by three-dimensional domain swapping. Dimerization is known to occur in the OmpR/PhoB subfamily of response regulators upon activation but has previously only been structurally characterized for isolated receiver domains. The RegX3 dimer has a bipartite intermolecular interface, which buries 2357 A(2) per monomer. The two parts of the interface are between the two receiver domains (dimerization interface) and between a composite receiver domain and the effector domain of the second molecule (interdomain interface). The structure provides support for the importance of threonine and tyrosine residues in the signal transduction mechanism. These residues occur in an active-like conformation stabilized by lanthanum ions. In solution, RegX3 exists as both a monomer and a dimer in a concentration-dependent equilibrium. The dimer in solution differs from the active form observed in the crystal, resembling instead the model of the inactive full-length response regulator PhoB.
King-Scott
Jack
J
EMBL-Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603, Hamburg, Germany.
Nowak
Elzbieta
E
Mylonas
Efstratios
E
Panjikar
Santosh
S
Roessle
Manfred
M
Svergun
Dmitri I
DI
Tucker
Paul A
PA
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods; D030562:Databases, Protein; D019281:Dimerization; D007477:Ions; D007811:Lanthanum / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013912:Threonine / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
D001426:Bacterial Proteins; D007477:Ions; C110608:RegX3 protein, Mycobacterium; C061278:PhoB protein, Bacteria; D013912:Threonine; D014443:Tyrosine; D007811:Lanthanum