Research Abstract:
Our research group is focused on understanding surveillance processes of the immune system, and the sabotage mechanisms used by pathogens to evade detection and host-mediated elimination. We use the techniques of protein biochemistry, x-ray crystallography and computational biology to determine the three-dimensional structures of proteins and investigate their macromolecular interactions. Current interests of the lab include proteins associated with classical MHC antigen processing and presentation pathways, non-classical MHC family members, and natural killer cell activating and inhibitory receptors. We also actively studying a number of virally encoded proteins that enable host immune evasion. Large-DNA viruses (i.e. herpesviruses and poxviruses) have evolved a myriad of strategies that include the sabotage of antigen processing, the molecular mimicry of host signaling molecules, and the sequestration of cytokines and chemokines by novel decoy receptors. Our approach to investigate these systems is based on the production of large quantities of soluble protein in heterologous expression systems, allowing for cognate ligand/ receptor discovery, biophysical interaction analyses, high-resolution structure determinations, and targeted functional studies. Together, these approaches provide a wealth of information on the basic tools with which the immune system operates.
Selected Publications:
Alexander JM, Nelson CA, van Berkel V, et al. Structural basis of chemokine sequestration by a herpesvirus decoy receptor. Cell 2002 111:343-356.
Brett TJ, Traub LM, Fremont DH. Accessory protein recruitment motifs in clathrin-mediated endocytosis. Structure 2002 10:797-809.
Smith HRC, Heusel JW, Mehta IK, et al. Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci USA 2002 99:8826-8831.
Kersh GJ, Miley MJ, Nelson CA, et al. Structural and functional consequences of altering a peptide MHC anchor residue. J Immunol 2001 166:3345-3354.
Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity. J Clin Invest 2001 108:971-979.
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