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Journal of Undergraduate Research

Keywords

Phosducin, Pd, N-terminus, C-terminus, heterotrimeric G-proteins, Gabg

College

Physical and Mathematical Sciences

Department

Chemistry and Biochemistry

Abstract

Cells use heterotrimeric G-proteins (Gabg) to transduce extracellular signals into intracellular messages. A hormone or other signal molecule binds to a seven trans-membrane receptor on the cell’s surface causing the receptor to change shape. On the inside of the cell this conformational change causes Gabg to split into a Ga subunit and a Gbg subunit complex. Both Ga and Gbg activate effector enzymes that determine the cellular response to the signal molecule. Phosducin (Pd) is a G-protein regulator that works by binding to the Gbg subunit complex and blocking Gbg function in three ways: 1) It blocks reassociation with Ga, a step necessary for reactivation of Gabg by receptors, 2) It blocks Gbg activation of effector enzymes, and 3) It dissociates Gbg from its functional place on the cell membrane. Pd has two domains which bind to Gbg: an N-terminus domain (Pd-N) which accounts for 2/3 of binding and a C-terminus domain (Pd-C) which accounts for 1/3. X-ray crystal studies of the Pd:Gbg complex have shown that Pd-N binds to the same surface as Ga, and that Pd-C covers the area which allows Gbg to bind back to the plasma membrane (1). This suggests that Pd-N is responsible for competing with Ga for Gbg binding (2) and that Pd-C is responsible for dissociating the Pd:Gbg from the membrane. However, there has been some data which suggest that the Pd-C, not Pd-N, competes with Ga for binding of Gbg (3). My research was designed to test whether the N-terminus or the C-terminus domain competes with Ga for binding of Gbg.

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