Structural Studies of  Chemokines and Chemokine Receptors

  

Illustration of  the activation of a chemokine receptor by its ligand, followed by desensitization and internalization. The final version of record is available at www.biochemj.org.

 

 

Our laboratory studies the relationship between the structure and function of chemokines and their receptors.  On the chemokine side, mutagenesis and structural studies are used to determine how chemokines bind and activate their G protein-coupled receptors. We are particularly interested in determining changes to specific chemokines that convert them into antagonists.  We also study chemokine  homo and heteroligomerization, their interaction with  glycosaminoglycans and the functional consequences of these interactions. Finally, we are studying the interaction of chemokines with viral chemokine binding proteins which bind a broad spectrum of chemokines with high affinity and effectively neutralize their function.  The work involves structural approaches (NMR and X-ray, other biophysical methods), biochemical and cell based assays, and in vivo studies.

More recently we have been focusing on the receptors.  We are using a number of strategies to obtain high levels of receptor for biophysical studies to understand conformational changes associated with receptor activation and antagonism, and ultimately for structural studies  of ligand:receptor complexes.

Techniques: X-ray crystallography, NMR, fluorescence, CD, H/D exchange mass spectrometry, other biophysical methods, cell based assays, molecular biology, phage display,  protein expression in a variety of systems