Researchers at Yale and the Salk Institute have determined the structure of a set of proteins called the Arp2/3 complex that helps cells move, paving the way for understanding how cells find bacteria and protect against infections.
“This is a dream come true to see the structure of this important protein complex in such detail,” said principal investigator Thomas Pollard, professor of molecular, cellular and developmental biology at Yale.
Published in the November 23 issue of Science, the study describes the atomic structure of the Arp2/3 complex for the first time. “Knowledge of the three-dimensional structure not only provides key insights about Arp2/3 complex, but it will also elevate the level of research on cellular movements for years to come,” said Pollard.
The Arp2/3 complex is one of the largest asymmetrical protein structures to be determined by x-ray crystallography at a very high resolution. The complex is made up of seven different proteins and is responsible for initiating the assembly of the protein actin into filaments at the front end of a moving cell. This growth of actin filaments is called polymerization and is believed to push the front of the cell forward, allowing it to move.
Pollard said the classic example of such movements is the locomotion of amoeba. Many human cells rely on the same mechanism. For example, protective white blood cells use actin polymerization to move to the sites of infection. Similarly, during the development of the human brain, nerve cells use actin polymerization to grow at least one million miles of long, thin cellular processes (axons and dendrites) that form the connections between nerve cells and between nerve cells and muscles.
Pollard said that in order for the cells to know in which direction to move, chemicals in the environment pass messages to the Arp2/3 complex, which interprets the messages that orient the nerves and other cells.
“Actin and Arp2/3 complex work like a peculiar motor in a car to make the cell move forward,” said Pollard. “Rather than turning wheels, the filaments grow like branches of a bush to push the cell forward. Arp2/3 complex is very ancient, having evolved in primitive cells well over one billion years ago.”
Pollard’s laboratory discovered the complex in 1994 and contributed to many of the observations that have made the Arp2/3 complex the center of attention in the cell movement field in recent years. Pollard’s laboratory also developed methods to make large quantities of highly purified Arp2/3 complex from the cow thymus gland. They discovered that this preparation forms crystals suitable for x-ray crystallography.
Other researchers on the study include Senyon Choe, Donald A. Kaiser, and Kirsl Turbedsky of the Salk Institute for Biological Studies; Robert C. Robinson of Uppsala University in Sweden; Jean-Baptiste Marchand of Avidis, Bipole Clermont-Limagne in France; and Henry N. Higgs of Dartmouth College.