Binding of Nucleocapsid Domain of HIV Gag Protein to Actin

Abstract

There has been a growing interest in the role of actin in the pathway of HIV infection: entry of HIV into cells involves a hijacking of the actin cytoskeleton, and nuclear migration of the virus requires actin. It was shown that the nucleocapsid domain (NC) of retroviral Gag protein can be associated with F-actin in a dose-dependent fashion in vitro and suggested that the interaction between HIV Gag and the actin cytoskeleton through the NC domain may play an important role in HIV assembly (Iyengar et al., 1998; Liu et al., 2009).However, the specificity of this interaction has never been established.We have used electron microscopy and the IHRSR method to reconstruct actin filaments decorated with the NC domain of HIV-1. We see strong and specific binding of this 55 residue NC domain to F-actin. Work is in progress to bring the resolution of this complex to the near-atomic level of resolution that we have now achieved for pure F-actin using a Titan Krios robotic microscope equipped with a direct electron detector. Exploring the interaction of HIV NC with actin could open up completely new areas in understanding HIV pathogenesis as well as in developing new drug targets.Reference ListIyengar,S., Hildreth,J.E., and Schwartz,D.H. (1998). Actin-dependent receptor colocalization required for human immunodeficiency virus entry into host cells. J. Virol. 72, 5251-5255. Liu,Y., Belkina,N.V., and Shaw,S. (2009). HIV infection of T cells: actin-in and actin-out. Sci. Signal. 2, e23.