Dr Ken Scott

Senior Lecturer

Molecular, Cellular & Developmental Biology

Phone: 09-3737599 x88240
Rm 256
Email: k.scott@auckland.ac.nz

Structure and Function of DING Proteins

DING proteins are ubiquitous, occurring in plants, animals, fungi and bacteria. The name comes from a strongly-conserved N-terminal sequence. They are associated with a number of diseases, including rheumatoid arthritis, lithiasis, cancer and viral infections, particularly HIV. Despite this association, no human, and indeed no eukaryotic, DING genes have been definitively identified, leading to a suggestion that eukaryotic DING proteins arise from bacterial infection or symbiosis.

DING genes have been identified in Pseudomonas and related bacteria. This laboratory was the first to clone and express such a gene, from Pseudomonas fluorescens, and a high-resolution protein structure was obtained. In common with most DING proteins, PfluDING binds phosphate ions with high affinity. It is expressed by P.fluorescens in response to low environmental phosphate, and forms part of a bacterial phosphate-scavenging system. It also replicates the functions of eukaryotic DING isolates, promoting cell growth, inhibiting the crystal nucleation that leads to kidneystone formation, and inhibiting HIV gene transcription in model systems.

Anti-HIV activity is an expanding research field, with a DING isolate from the medicinal herb, St John’s Wort first shown to have this antitranscriptional activity on HIV, and recent evidence that a human lymphocyte-derived HIV resistance factor is in fact a DING protein, operating in the same way. We are pursuing this aspect of DING research, concentrating on recombinant bacterial DING protein variants, using site-directed mutagenesis to improve and characterize transcriptional inhibition of HIV.

DING proteins also act as virulence factors for pathogenic Pseudomonas aeruginosa, and we are examining the roles of these proteins in phosphate acquisition, adherence to human epithelial cells, and gene regulation in the target cells.

Many DING proteins have hydrolytic enzymic activity, though in some cases it is not clear what role this has. We are interested in the structure and function of these enzymes.

PhD Students

Andrew Suh - Anti-HIV activity of DING proteins

Megha Shah - DING proteins as bacterial virulence factors

fig1_new_small_

The structure of the 39kDa PfluDING protein, and its genetic truncation, resulting in a single- domain 17kDa protein retaining many of the functions of the whole molecule (Ahn et al., 2007).

Selected Recent Publications

A Berna, K Scott, E Chabrière and F Bernier. (2009). The DING family of proteins: ubiquitous in eukaryotes, but where are the genes?. Bioessays 31, 570-580..

A Berna, F Bernier, E Chabrière, M Elias, K Scott and A Suh. (2009). For Whom the Bell Tolls? DING Proteins in Health and Disease.. Cell. Mol. Life Sci. 66, 2205-2218.

D Liebschner, M Elias, B Fournier, K Scott, S Moniot, C Jelsch, B Guillot, C Lecompte and E Chabriere. (2009). Elucidation of the phosphate binding mode of DING proteins revealed by sub-Ångstrom X-ray crystallography.. J. Amer. Chem. Soc. 131, 7879-7886. .

A Berna, F Bernier, E Chabrière, T Perera and K Scott. (2008). DING proteins; novel members of a prokaryotic phosphate-binding protein superfamily which extends into the eukaryotic kingdom.. Intl. J. Biochem. Cell Biol. 40, 170-175..

Ahn, S., Moniot, S., Elias, M., Chabrière, E., Kim, D. and Scott, K. (2007). Structure-function relationships in a bacterial DING protein.. FEBS Lett. 581, 3455-3460..

Zhang, X-X., Scott, K., Meffin, R. and Rainey, P.B (2007). Genetic characterization of psp encoding the DING protein in Pseudomonas fluorescens SBW25.. BMC Microbiol.7, 114..

Perera, T., Berna, A., Scott, K., Lemaitre-Guillier, C. and Bernier, F. (2007). Proteins related to St John’s Wort p27SJ, a suppressor of HIV-1 expression, are ubiquitous in plants.. Phytochemistry 69, 865-872..

K Scott and L Wu. (2005). Functional properties of a recombinant bacterial DING protein: comparison with a homologous human protein. Biochim. Biophys. Acta 1744, 234-244.. Biochim. Biophys. Acta 1744, 234-244..

L Adams, S Davey and K Scott. (2002). The DING protein: An autocrine growth-stimulatory protein related to the human synovial stimulatory protein.. Biochim. Biophys. Acta 1586 254-264..