5ED4

Structure of a PhoP-DNA complex

Summary for 5ED4

• Entry DOI: 10.2210/pdb5ed4/pdb
• Descriptor: Response regulator, DNA (26-MER), CALCIUM ION, ... (7 entities in total)
• Functional Keywords: protein-dna complex, winged helix-turn-helix, direct repeat, tandem dimer, transcription-dna complex, transcription/dna
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 8
• Total formula weight: 143959.57

Authors

Wang, S. (deposition date: 2015-10-20, release date: 2016-04-27, Last modification date: 2023-09-27)

Primary citation

He, X.,Wang, L.,Wang, S.
Structural basis of DNA sequence recognition by the response regulator PhoP in Mycobacterium tuberculosis.
Sci Rep, 6:24442-24442, 2016

PubMed Abstract: The transcriptional regulator PhoP is an essential virulence factor in Mycobacterium tuberculosis, and it presents a target for the development of new anti-tuberculosis drugs and attenuated tuberculosis vaccine strains. PhoP binds to DNA as a highly cooperative dimer by recognizing direct repeats of 7-bp motifs with a 4-bp spacer. To elucidate the PhoP-DNA binding mechanism, we determined the crystal structure of the PhoP-DNA complex. The structure revealed a tandem PhoP dimer that bound to the direct repeat. The surprising tandem arrangement of the receiver domains allowed the four domains of the PhoP dimer to form a compact structure, accounting for the strict requirement of a 4-bp spacer and the highly cooperative binding of the dimer. The PhoP-DNA interactions exclusively involved the effector domain. The sequence-recognition helix made contact with the bases of the 7-bp motif in the major groove, and the wing interacted with the adjacent minor groove. The structure provides a starting point for the elucidation of the mechanism by which PhoP regulates the virulence of M. tuberculosis and guides the design of screening platforms for PhoP inhibitors.

PubMed: 27079268
DOI: 10.1038/srep24442

Experimental method

X-RAY DIFFRACTION (2.4 Å)