How do gingipains recognise their host cell targets?

Summary

Porphyromonas gingivalis is a gram-negative, rod-shaped anaerobic pathogenic bacterium that found in the oral cavity.

Supervisor(s)

Associate Professor Charles Collyer

Research Location

School of Molecular Bioscience

Program Type

Masters/PHD

Synopsis

Porphyromonas gingivalis is a gram-negative, rod-shaped anaerobic pathogenic bacterium that found in the oral cavity. It causes many forms of periodontal disease and infections in respiratory tract and the colon. Gingipains are outer membrane associated cysteine proteinases that are secreted by P.gingivalis, that act in degradation of host tissues, cell invasion, modulating immune response  and deregulation of cytokine networks. The research conducted in the Collyer Lab has been focusing on the cleaved adhesin modules in haemagglutinin/adhesin (HA) regions of gingipains expressed by P.gingivalis (Li et al., 2010). Hemoglobin, fibrinogen and serum albumin are some of the known targets of the adhesin modules. There are five classes of cleaved adhesin modules found in gingipains, and the crystal structures of two modules have recently been determined (Li et al., 2011). Moreover, both modules have been found to be capable of inducing hemolysis. It is predicted that all five classes of modules will possess the same principal feature, which is the ß-jelly roll-barrel that observed in the two solved modules (Li & Collyer, 2011). Recently a new domain of the gingipains (designated DUF2436) of hereto unknown structural class has been identified by the Collyer laboratory. Functional and structural studies will be conducted to define its role in gingipain biology. Preliminary data suggest that the five structural classes of P.gingivalis adhesion modules and their interactions with host proteins are different, therefore the variability of adhesin module functions will be investigated. How the newly discovered DUF modules contribute to the functions of gingipains will also be investigated. Binding studies and cellular assays (Yun et al. 2012) will indicate the effects of structural variations in adhesion and DUF modules on their target specificities. Mutants of adhesin modules will be made by PCR, and their activities tested to highlight putative binding motifs. Structural techniques such as X-ray crystallography will be used to improve the resolution of the existing models and hence define the genetic similarities and differences which impart cooperative and differential binding to target host protein.<!--EndFragment-->

Additional Information

Protein Crystallography and Protein Chemistry

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Keywords

Therapeutics & adverse drug effects, Infectious diseases, Cell biology, Infection & immunity, Pharmacology & therapeutics

Opportunity ID

The opportunity ID for this research opportunity is: 29