Peter Ren L&S Sciences
Investigating Allostery in the T4 Bacteriophage Clamp Loader
The AAA+ proteins (ATPases Associated with a variety of cellular Activities) are a highly diverse and ancient protein superfamily present in all organisms and are involved in such processes such as DNA replication, protein degradation, and metal insertion in protein synthesis. AAA+ proteins have some conserved features, including an oligomeric ring structure that exhibits inter-protomer cooperativitythat is to say, the hydrolysis of ATP in one subunit causes the preferential hydrolysis of ATP in the other subunits, making for a more efficient channeling of energy from ATP when switching states. While the existence of this cooperativity in AAA+ proteins is highly common, there is still little to no understanding about how the other subunits are able to detect the hydrolysis of ATP. In order to study allostery in AAA+ proteins, I will focus my research on one particular member of this superfamilythe T4 bacteriophages DNA clamp loader protein. Through computational and experimental methods, I hope to unwind the mystery of the structure-function relationship of this protein.