Wednesday, July 1, 2015
“Structural Investigation of Retroviral Fusion and Integration Machineries by High-Resolution CryoEM. ”
Dmitry Lyumkis, Salk Institute for Biological Studies
Retroviruses use intricate mechanisms to enter into target host cells in order to establish permanent and irreversible infection. Several important machineries play fundamental roles in the retroviral infectivity lifecycle. Fusion between viral and cellular membranes is catalyzed by Envelope (Env), which enables retroviral entry into hosts. Once inside the host, retroviral RNA must be converted into DNA and then integrated into host genomic DNA to establish permanent infection. The retroviral integration process is catalyzed by an oligomeric form of Integrase (IN). I will present two stories, which employ recent advances in cryoEM technologies, including both high-resolution and heterogeneity analysis, to describe these two stages of the retroviral lifecycle. First, I will present the cryoEM structure of the HIV-1 Env trimer, the viral surface glycoprotein that is responsible for HIV-1 entry into host cells and the sole target for broadly neutralizing human antibodies. Second, I will describe the cryoEM structure of the Mouse Mammary Tumor Virus (MMTV) integration complex, a 300 kDa octameric complex of IN and viral DNA that is responsible for establishing permanent infection in the host. These results pave the way for detailed structural and functional studies of the retroviral life cycle.