6DT4

1.8 Angstrom Resolution Crystal Structure of cAMP-Regulatory Protein from Yersinia pestis in Complex with cAMP

Summary for 6DT4

• Entry DOI: 10.2210/pdb6dt4/pdb
• Descriptor: Cyclic AMP receptor protein, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: structural genomics, center for structural genomics of infectious diseases, csgid, dna-binding, camp, dna binding protein
• Biological source: Yersinia pestis CO92
• Total number of polymer chains: 2
• Total formula weight: 48628.04

Authors

Minasov, G.,Shuvalova, L.,Kiryukhina, O.,Ritzert, J.T.H.,Anderson, W.F.,Satchell, K.J.F.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2018-06-15, release date: 2018-06-27, Last modification date: 2023-10-11)

Primary citation

Ritzert, J.T.,Minasov, G.,Embry, R.,Schipma, M.J.,Satchell, K.J.F.
The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in Yersinia pestis during Planktonic Growth and Growth in Biofilms.
Mbio, 10:-, 2019

PubMed Abstract: Cyclic AMP (cAMP) receptor protein (Crp) is an important transcriptional regulator of Expression of increases during pneumonic plague as the pathogen depletes glucose and forms large biofilms within lungs. To better understand control of Crp, we determined a 1.8-Å crystal structure of the protein-cAMP complex. We found that compared to Crp, C helix amino acid substitutions in Crp did not impact the cAMP dependency of Crp to bind DNA promoters. To investigate Crp-regulated genes during plague pneumonia, we performed RNA sequencing on both wild-type and Δ mutant bacteria growing in planktonic and biofilm states in minimal media with glucose or glycerol. Crp was found to dramatically alter expression of hundreds of genes in a manner dependent upon carbon source and growth state. Gel shift assays confirmed direct regulation of the and promoters, and Crp was then linked to growth on maltose as a sole carbon source. Iron regulation genes and were found to be indirectly regulated by Crp. A new connection between carbon source and quorum sensing was revealed as Crp was found to regulate production of acyl-homoserine lactones (AHLs) through direct and indirect regulation of genes for AHL synthetases and receptors. AHLs were subsequently identified in the lungs of -infected mice when expression was highest in biofilms. Thus, in addition to the well-studied gene, other Crp-regulated genes likely have important functions during plague infection. Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen requires this global regulator to survive in blood, skin, and lungs. During disease progression, this organism adapts to changes within these niches. In addition to regulating genes for metabolism of nonglucose sugars, we found that Crp regulates genes for virulence, metal acquisition, and quorum sensing by direct or indirect mechanisms. Thus, this single transcriptional regulator, which responds to changes in available carbon sources, can regulate multiple critical behaviors for causing disease.

PubMed: 31744922
DOI: 10.1128/mBio.02613-19

Experimental method

X-RAY DIFFRACTION (1.8 Å)