F A C U L T Y P R O F I L E
Fan, Qing R. Ph.D.
Structural biology; cell surface receptor-ligand recognition.
Office: Physicians & Surgeons| 7th floor | Room 430
Our laboratory studies the molecular mechanisms by which G-protein coupled receptors (GPCRs) transmit signals across biological membranes. GPCRs represent the superfamily of transmembrane receptors that signal through heterotrimeric G-proteins. GPCRs recognize a diverse array of ligands, and are the targets for 50-60% of clinical drugs. We combine x-ray crystallography with various biochemical techniques to study these receptors with two general goals: (1) to determine the specificity of receptor-ligand interactions, and (2) to identify receptor activation mechanisms.
Recently, we determined the crystal structure of human FSH bound to the extracellular hormone-binding domain of its receptor (FSHRHB). The FSH-FSHRHB complex structure shows the hormone bound in a hand-clasp fashion to the inner surface of a curved receptor ectodomain. Analysis of the hormone-receptor interface in the structure indicates that all glycoprotein hormones bind to their receptors in a common mode, and binding specificity is jointly mediated by the common α- and hormone-specific β-subunits. The FSH-FSHRHB complex structure provides a molecular understanding of their interactions, which may be utilized to design FSH mimics as alternative agonists and contraceptive antagonists.
1. Fan, Q. R. and Hendrickson, W. A. (2008). Comparative structural analysis of the binding domain of the follicle stimulating hormone receptor. Proteins 72, 393-401.
2. Fan, Q. R. and Hendrickson, W. A. “Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor” Mol. Cell. Endocrinol. 260-262, 73-82 (2007).
3. Fan, Q. R. and Hendrickson, W. A. “Structure of human follicle-stimulating hormone in complex with its receptor” Nature 433, 269-277 (2005).
4. Fan, Q. R., Long, E. O. and Wiley, D. C. “Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1 bound to its class I MHC ligand” Nature Immunology 2, 452-460 (2001).
5. Fan, Q. R. and Wiley, D. C. “Structure of human leukocyte antigen (HLA)-Cw4, a ligand for the KIR2D natural killer cell inhibitory receptor” J. Exp. Med. 190, 113-123 (1999).
6. Fan, Q. R., Mosyak, L., Winter, C. C., Wagtmann, N., Long, E. O. and Wiley, D. C. “Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors” Nature 389, 96-100 (1997).