Krishna Rajarathnam, Ph.D.

Associate Professor, Dept. Biochemistry and Molecular BioloDr. Rajarathnamgy, Dept. Microbiology and Immunology, Sealy Center for Structural Biology and Molecular Biophysics

 

Research Activities

The immune surveillance system is highly evolved to counter infectious pathogens and other physiological insults by recruiting leukocytes in a timely and coordinated manner. This remarkable response is mediated by a family of proteins called chemokines, but paradoxically, an imbalance in the chemokine response can also result in damage to healthy tissue, leading to numerous inflammatory diseases. Chemokines execute their function by binding to both G protein-coupled receptors (GPCRs) on leukocytes and glycosaminoglycans (GAGs) on the endothelial cells and the extracellular matrix. We are interested in understanding the structural basis of how these interactions mediate leukocyte recruitment. Ultimately we are interested in using this information for designing structure-aided peptidomimetics and protein therapeutics for inflammatory diseases.

Selected Publications

  1. Crump, M., Rajarathnam, K., Kim, K-S., Clark-Lewis, I., and Sykes, B. D. Solution Structure of Eotaxin: a Chemokine that Selectively Recruits Eosinophils in Allergic Inflammation J. Biol. Chem. 273:22471-22479 (1998).
  2. Rajarathnam, K., Li, Y., Rohrer, T., and Gentz, R. Solution Structure and Dynamics of Myeloid Progenitor Inhibitor Factor-1 (MPIF-1): A Novel Monomeric CC Chemokine J. Biol.Chem, 276:4909-4916 (2001).
  3. Rajarathnam, K. Designing Decoys for Chemokine-Chemokine Receptor Interaction. Current Pharmaceutical Design 8:2159-2169 (2002).
  4. Fernando, H., Chin, C., Rösgen, J., and Rajarathnam, K. Dimer Dissociation is Essential for Interleukin-8 (IL-8) Binding to CXCR1 Receptor J. Biol. Chem. 279:36175-36178 (2004).
  5. Chauhan, M., Rajarathnam, K., and Yallampalli, C. Characterization of the N-terminal domain of Calcitonin Gene Related Peptide Receptor Components Biochemistry 44:782-789 (2005)
  6. Rajagopalan, L., Rösgen, J., Bolen, W. D., and Rajarathnam, K. Novel use of an osmolyte to dissect thermodynamic linkages between receptor N-domain folding, ligand binding, and ligand dimerization in a chemokine-receptor system: Implications for in vivo regulation 44:12932-12939 (2005).
  7. Rajarathnam, K., Prado, G. N., Fernando, H., Clark-Lewis, I., Navarro, J. Probing receptor binding activity of interleukin-8 dimer using a disulfide trap. Biochemistry 45:7882-7888 (2006).
  8. Rajarathnam, K. A reply to 'A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation'. Nature Medicine 12:603-604 (2006).
  9. Rajagopalan, L. and Rajarathnam, K. Structural basis of chemokine receptor function – A model for binding affinity and ligand selectivity Bioscience Reports 26:325-339 (2006).
  10. Fernando, H., Nagle, G., and Rajarathnam, K. Thermodynamic Basis of Interleukin-8 Monomer Binding to the CXCR1 Receptor N-domain: An Isothermal Titration Calorimetry Study 274: 241-251 (2007).