Modeling Cells' Messengers
December 9, 2005
Humans have millions of cells to conduct the business of the body. By exchanging chemical signals, cells "talk" to each other to perform functions like regulating blood pressure, converting food into nutrition and sensing pain or danger.
Along this superhighway of communication, the family of G proteins is one of the most consequential messengers. G proteins have been implicated in the signaling for dozens of metabolic functions including blood pressure, blood clotting, sight and smell. Despite their centrality to the basic systems of life, many aspects of the G proteins' structure and function remain a mystery.
Now, John Tesmer, Life Sciences Institute Research Associate Professor and Associate Professor in UM Medical School's Department of Pharmacology, has captured a picture of these messengers in their active state, that is, in the act of conveying signals, at the cell membrane. The research was published today in the leading journal Science.
Tesmer's new study, which provides high resolution models of a G protein involved in blood clot formation, heart disease, and blood pressure, is the first molecular view of how these important proteins can be arranged at the cell membrane. Researchers can now target these protein complexes to try to develop new tools and therapeutic drugs for treating conditions like cardiovascular disease.
Using X-Ray crystallography, Tesmer determined the atomic structure of a G protein known as Gq when Gq is interacting with another important signaling protein called GRK2. Defects in either Gq or GRK2 lead to severe heart development defects. The atomic structure of these multiple molecular complexes are extremely difficult to obtain and this work represents an important step forward for capturing nature in action.
Crystallography is a technique which uses X-rays to develop 3-D pictures of macromolecules.
The paper "Snapshot of Activated G proteins at the Membrane: Structure of the G a q -GRK2-G bg Complex" by Tesmer, appears in the journal Science, December 9, 2005.
