3R0J

Structure of PhoP from Mycobacterium tuberculosis

Summary for 3R0J

• Entry DOI: 10.2210/pdb3r0j/pdb
• Descriptor: POSSIBLE TWO COMPONENT SYSTEM RESPONSE TRANSCRIPTIONAL POSITIVE REGULATOR PHOP, SULFATE ION, R-1,2-PROPANEDIOL, ... (4 entities in total)
• Functional Keywords: beta-alpha fold, winged helix-turn-helix, transcription regulator, dna binding, dna binding protein
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 56657.15

Authors

Menon, S.,Wang, S. (deposition date: 2011-03-08, release date: 2011-07-13, Last modification date: 2025-03-26)

Primary citation

Menon, S.,Wang, S.
Structure of the Response Regulator PhoP from Mycobacterium tuberculosis Reveals a Dimer through the Receiver Domain.
Biochemistry, 50:5948-5957, 2011

PubMed Abstract: The PhoP protein from Mycobacterium tuberculosis is a response regulator of the OmpR/PhoB subfamily, whose structure consists of an N-terminal receiver domain and a C-terminal DNA-binding domain. How the DNA-binding activities are regulated by phosphorylation of the receiver domain remains unclear due to a lack of structural information on the full-length proteins. Here we report the crystal structure of the full-length PhoP of M. tuberculosis. Unlike other known structures of full-length proteins of the same subfamily, PhoP forms a dimer through its receiver domain with the dimer interface involving α4-β5-α5, a common interface for activated receiver domain dimers. However, the switch residues, Thr99 and Tyr118, are in a conformation resembling those of nonactivated receiver domains. The Tyr118 side chain is involved in the dimer interface interactions. The receiver domain is tethered to the DNA-binding domain through a flexible linker and does not impose structural constraints on the DNA-binding domain. This structure suggests that phosphorylation likely facilitates/stabilizes receiver domain dimerization, bringing the DNA-binding domains to close proximity, thereby increasing their binding affinity for direct repeat DNA sequences.

PubMed: 21634789
DOI: 10.1021/bi2005575

Experimental method

X-RAY DIFFRACTION (2.5 Å)