Structure and Signaling Mechanisms of G Protein-Coupled and b-Arrestin-Biased Chemokine Receptors

IIG Seminar Most chemokine receptors are G Protein-Coupled Receptors (GPCRs), and are best known for their role in controlling cell migration in the context of immune system function. They are also implicated in many diseases particularly inflammatory diseases as well as cancer and HIV, making them important therapeutic targets. Recent structural and biophysical studies have revealed that the recognition interface between chemokines and receptors is very large and characterized by more complex epitopes than previously believed. In this presentation, our current understanding of how chemokines bind and activate their receptors will be described, as well mechanisms for inhibiting chemokine receptor signaling with orthosteric and allosteric ligands. Common and unique features of G protein-coupled versus b-arrestin-biased receptors will also be described, focusing on CXCR4 (a GPCR) and the b -arrestin-biased, atypical chemokine receptor 3 (ACKR3) both of which respond to the chemokine CXCL12. Dr. Handel received her PhD in Chemistry at the California Institute of Technology and then did a postdoc in biophysics/protein design at DuPont Merck Pharmaceuticals. After a brief period as a PI in the structural biology group at Dupont where she began investigating chemokines, she moved to Berkeley as an Assistant Professor, ultimately receiving tenure in the Dept. of Molecular and Cell Biology. She then moved to UC San Diego in 2005, joining the Dept of Pharmacology in the School of Medi...
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