|
|
Qing R. Fan, Ph.D.
Assistant Professor of Pharmacology and Pathology
|
Research
Summary
Structural biology; cell surface receptor-ligand recognition.
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.
|
Selected Publications:
1. Fan QR, Hendrickson WA. (2007) 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
2. Fan QR, Hendrickson WA. (2005) Structure of human follicle-stimulating hormone in complex with its receptor. Nature
433:269-277
3. Fan QR, Hendrickson WA. (2005) Structural biology of glycoprotein hormones and receptors. Endocrine
26:179-188
4. Fan QR, Long EO, Wiley DC. (2001) Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1 bound to its class I MHC ligand. Nature Immunology
2:452-460
5. Fan QR, Mosyak L, Winter CC, Wagtmann N, Long EO, Wiley DC. (1997) Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors. Nature 389
389:96-100
6. Fan QR, Wiley DC. (1999) Structure of human leukocyte antigen (HLA)-Cw4, a ligand for the KIR2D natural killer cell inhibitory receptor. J. Exp. Med.
190:113-123
7. Fan QR, Garboczi DN, Winter CC, Wagtmann N, Long EO, Wiley DC. (1996) Direct binding of a soluble natural killer cell inhibitory receptor to a soluble human leukocyte antigen-Cw4 class I major histocompatibility complex molecule. Proc. Natl. Acad. Sci. USA
93:7178-7183
8. Fan QR, Long EO, Wiley DC. (2000) Cobalt-mediated dimerization of the human natural killer cell inhibitory receptor. J. Biol. Chem.
93275:23700-23706
|
|
|
|
|
|
|
top
|
