Team of Boston Scientists Solve Structure of the Body's Most Abundant Protein.

Business/Technology Editors & Health/Medical Writers

WATERTOWN, Mass.--(BW HealthWire)--July 27, 2001

This week the journal Science will publish the research findings of a team of scientists at the not-for-profit Boston Biomedical Research Institute (BBRI) who have used a technique known as X-ray Crystallography to determine the molecular structure of actin, the most abundant protein in the human body. Actin molecules assemble to form filaments that work together with myosin to make our muscles contract. The dynamic assembly/disassembly of actin filaments, in concert with other proteins, underlies many other basic cellular processes such as cell movement, cell division, and changes in cell structure. Knowledge of actin's structure helps medical scientists to understand a myriad of functions in the human body and control disease processes such as cancer metastasis. Because it is such an important protein, scientists around the globe have been intensively studying actin for many years.

Led by Dr. Roberto Dominguez, the team at BBRI, including graduate student Ludovic Otterbein and Dr. Philip Graceffa, succeeded in mapping the key change in the actin atomic structure underlying the dynamic assembly/disassembly process. This was accomplished with the help of serendipity and collaboration, which often drive scientific advances. In order to study how actin regulates smooth muscle contraction, Dr. Graceffa labeled the actin with fluorescent probes. Graceffa found that one type of probe blocked actin's ability to form filaments. He realized that this information could be useful in his collaboration with Dominguez's crystallography group because filament formation has been an impediment to actin crystallization. Indeed, by employing Graceffa's modified actin, Otterbein and Dominguez succeeded in crystallizing the protein and solving its atomic structure, completing the project in less than three months.

X-ray Crystallography, which was used by Dr. Dominguez's team, involves passing intense X-ray beams through crystals of actin and employing complex mathematical procedures in order to define the exact position in space of each of actin's thousands of atoms. By "solving" the structure of a protein, scientists can learn how the protein functions, knowledge that is fundamental to rational drug design. "Actin interacts with more proteins than any other protein in the human body," says Dominguez, "It will now be possible to try to form crystals of actin in combination with many of these proteins, which will be useful in understanding basic biological functions."

Alongside these research findings, Science is publishing a "Perspective" about this work by Dr. Thomas Pollard, a professor at Yale University. Dr. Pollard has been one of the leaders in elucidating the mechanisms by which actin filaments form and dissociate, and the role which this process plays in cell movement.