University of Michigan' Researcher Provides Model of Cell's Messengers

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 U-M Medical School's Department of Pharmacology, has captured a picture of these messengers in their active state: when they are conveying signals at the cell membrane. The research was published this month in the journal Science.

Tesmer's study, which provides high-resolution models of one 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 tools and therapeutic drugs for treating conditions like cardiovascular disease.

Using X-Ray crystallography, Tesmer determined that the atomic structure of a G protein is interacting with an important signaling switch called GRK2.

Defects in either the protein or the switch could lead to severe heart development defects.

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 Dec. 9.