4LDZ

Crystal structure of the full-length response regulator DesR in the active state

Summary for 4LDZ

• Entry DOI: 10.2210/pdb4ldz/pdb
• Related: 4LE0 4LE1 4LE2
• Descriptor: Transcriptional regulatory protein DesR, MAGNESIUM ION, BERYLLIUM TRIFLUORIDE ION, ... (6 entities in total)
• Functional Keywords: response regulator, two-component system, transcription factor, receiver domain, dna binding domain, phosphorylation, active state, dna binding protein
• Biological source: Bacillus subtilis subsp. subtilis
• Cellular location: Cytoplasm : O34723
• Total number of polymer chains: 2
• Total formula weight: 45396.63

Authors

Trajtenberg, F.,Larrieux, N.,Buschiazzo, A. (deposition date: 2013-06-25, release date: 2014-07-16, Last modification date: 2024-02-28)

Primary citation

Trajtenberg, F.,Albanesi, D.,Ruetalo, N.,Botti, H.,Mechaly, A.E.,Nieves, M.,Aguilar, P.S.,Cybulski, L.,Larrieux, N.,de Mendoza, D.,Buschiazzo, A.
Allosteric activation of bacterial response regulators: the role of the cognate histidine kinase beyond phosphorylation.
MBio, 5:e02105-e02105, 2014

PubMed Abstract: Response regulators are proteins that undergo transient phosphorylation, connecting specific signals to adaptive responses. Remarkably, the molecular mechanism of response regulator activation remains elusive, largely because of the scarcity of structural data on multidomain response regulators and histidine kinase/response regulator complexes. We now address this question by using a combination of crystallographic data and functional analyses in vitro and in vivo, studying DesR and its cognate sensor kinase DesK, a two-component system that controls membrane fluidity in Bacillus subtilis. We establish that phosphorylation of the receiver domain of DesR is allosterically coupled to two distinct exposed surfaces of the protein, controlling noncanonical dimerization/tetramerization, cooperative activation, and DesK binding. One of these surfaces is critical for both homodimerization- and kinase-triggered allosteric activations. Moreover, DesK induces a phosphorylation-independent activation of DesR in vivo, uncovering a novel and stringent level of specificity among kinases and regulators. Our results support a model that helps to explain how response regulators restrict phosphorylation by small-molecule phosphoryl donors, as well as cross talk with noncognate sensors.

PubMed: 25406381
DOI: 10.1128/mBio.02105-14

Experimental method

X-RAY DIFFRACTION (2.31 Å)