Glucagon As Family B GPCR Model
Among GPCRs, high-resolution structural information is currently
available only for rhodopsin, a highly specialized visual pigment
which is a prototype of the Family A class. The Family B GPCRs,
which are defined by long extracellular N-terminal tails, comprise
receptors for up to fifty peptide hormones. The glucagon receptor,
which is responsible for the maintenance of normal plasma glucose
levels required for an organism's survival, is a member of this
family.
Little is known about the structural elements of Family B GPCRs that
define peptide affinity and specificity, and the molecular mechanism
of receptor activation. Our long-term objective is to elucidate the
molecular mechanism of signal transduction by peptide hormone receptors.
We study the glucagon receptor as a model system for the Family B GPCR's,
and we attempt to obtain site-specific structural information about the
receptor using an interdisciplinary approach. Our work on the glucagon
receptor is carried out in collaboration with Dr. Cecille Unson and Prof.
Bruce Merrifield at The Rockefeller University.
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