Forum 03/22/2007

“The structure of hexameric assemblies of full-length HIV-1 CA:  A model for the mature capsid lattice”

Barbie Pornillos – Department of Cell Biology, The Scripps Research Institute, La Jolla, CA

The capsids of mature retroviruses perform the essential function of organizing the genome for efficient replication.  These capsids are modeled as fullerene structures composed of closed hexameric arrays of the viral CA protein, but a high-resolution structure of the lattice has remained elusive.   A three-dimensional map derived by electron cryo-crystallography combined with high-resolution domain structures yielded an unambiguous model for full-length CA, which revealed three important protein-protein assembly interfaces required for capsid formation.  Each CA hexamer is composed of an inner ring of six N-terminal domains and an outer ring of C-terminal domains that form dimeric linkers connecting neighboring hexamers.  Interactions between the two domains of CA further stabilize the hexamer, and provide a structural explanation for the mechanism of action of known HIV-1 assembly inhibitors.