PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Protein Folding and Misfolding: It's the Journey, Not the Destination
March 2015
CCR5 and HIV Infection
January 2015
HIV/AIDS: Pre-fusion Env Exposed
January 2015
HIV/AIDS: Slide to Enter
January 2015
Updating ModBase
January 2015
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Bacterial CDI Toxins
June 2014
Immunity: One Antibody to Rule Them All
June 2014
Virology: A Bat Influenza Hemagglutinin
March 2014
Virology: Making Sensitive Magic
March 2014
Virology: Visualizing Cyanophage Assembly
March 2014
Virology: Zeroing in on HBV Egress
March 2014
March 2014
Cas4 Nuclease and Bacterial Immunity
February 2014
Microbial Pathogenesis: A GNAT from Pseudomonas
February 2014
Microbial Pathogenesis: Targeting Drug Resistance in Mycobacterium tuberculosis
February 2014
Microbiome: The Dynamics of Infection
September 2013
Membrane Proteome: A Funnel-like Viroporin
August 2013
Infectious Diseases: A Pathogen Ubiquitin Ligase
May 2013
Infectious Diseases: A Shared Syringe
May 2013
Infectious Diseases: Determining the Essential Structome
May 2013
Infectious Diseases: Targeting Meningitis
May 2013
NDM-1 and Antibiotics
May 2013
Bacterial Hemophores
January 2013
Microbial Pathogenesis: Computational Epitope Prediction
January 2013
Microbial Pathogenesis: Influenza Inhibitor Screen
January 2013
Microbial Pathogenesis: Measles Virus Attachment
January 2013
Microbial Pathogenesis: NEAT Iron
January 2013
Membrane Proteome: Sphingolipid Synthesis Selectivity
December 2012
A signal sensing switch
September 2012
Gauging needle structure
July 2012
Anthrax Stealth Siderophores
June 2012
A Pseudomonas L-serine dehydrogenase
May 2012
Pilus Assembly Protein TadZ
April 2012
Making Lipopolysaccharide
January 2012
Superbugs and Antibiotic Resistance
December 2011
A change to resistance
November 2011
An effective and cooperative dimer
November 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
Breaking down the defenses
September 2011
Moving some metal
August 2011
Capsid assembly in motion
April 2011
Know thy enemy … structurally
October 2010
Treating sleeping sickness
May 2010
Bacterial spore kinase
April 2010
Hemolysin BL
January 2010
Unusual cell division
October 2009
Anthrax evasion tactics
September 2009
Toxin-antitoxin VapBC-5
September 2009
Antibiotic target
August 2009
July 2009
Tackling influenza
June 2009
You look familiar: the Type VI secretion system
June 2009
Unique SARS
April 2009
Anthrax stealth molecule
March 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Antiviral evasion
October 2008
SARS connections
September 2008
SARS Coronavirus Nonstructural Protein 1
June 2008

Research Themes Infectious diseases

Quorum Sensing: A Groovy New Component

SBKB [doi:10.1038/sbkb.2014.214]
Featured Article - August 2014
Short description: A first-in-family structure of a Pseudomonas-specific protein provides clues to its role in quorum sensing.

Surface representation of PA3611, color-coded for residue conservation (green, low; magenta, high). Highly conserved residues lie primarily on one side of PA3611 and line a prominent groove. Figure courtesy of Debanu Das.

Pseudomonas aeruginosa is a pervasive environmental pathogen and leading cause of nosocomial infection, especially in immunocompromised individuals. P. aeruginosa controls expression of its virulence factors using quorum sensing (QS), the process by which small secreted signaling molecules facilitate monitoring of bacterial cell density. Components of QS systems and the virulence factors they regulate are potential targets for antimicrobial agents, but many are likely hidden among the numerous P. aeruginosa proteins that have not been functionally or structurally characterized.

Das and colleagues (PSI JCSG) have now determined the crystal structure of PA3611 (PDB 3NPD), a ∼14-kDa protein thought to be upregulated in QS, based on its secretion by wild type P. aeruginosa PAO1 but not by attenuated, QS-defective mutant strains. This is the first structural representative of the PF13652 (DUF4146) protein family, a group of Pseudomonas-specific single-domain proteins of unknown function. The crystal structure shows a twisted antiparallel β-sheet flanked by α-helices. Residue conservation analysis using CONSURF revealed a cluster of highly conserved surface residues on one side of the protein, most of which line a prominent groove.

Although sequence analysis of PA3611 using Position-Specific Iterated-BLAST failed to identify any non-Pseudomonas homologs, a search for similar structures using the FATCAT flexible alignment mode identified the C-terminal domain of Escherichia coli Era GTPase, a prokaryotic type KH domain (KH-domain type II) involved in protein and RNA binding. Comparison of the PA3611 and Era KH structures shows that, despite considerable differences in helix positions, surface residues along a helix-turn-helix motif have similar side chain chemistry. Thus, both structures share a basic region that is thought to mediate RNA binding in the Era KH domain.

Although further analysis is needed to determine the binding partners and exact role of PA3611, genomic computational analysis by the authors predicted that PA3611 is a virulence factor, with potential functional or physical interaction with PotD (PA3610), a substrate-binding protein in the polyamine uptake system implicated in QS.

Anita M. Engh


  1. D. Das et al. Crystal structure of a putative quorum sensing-regulated protein (PA3611) from the Pseudomonas-specific DUF4146 family.
    Proteins. 82, 1086-92 (2014). doi:10.1002/prot.24455

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health