Interaction with simian Hck tyrosine kinase reveals convergent evolution of the Nef protein from simian and human immunodeficiency viruses despite differential molecular surface usage

Abstract

Simian and human immunodeficiency virus type 1 (SIV and HIV-1) Nef proteins are thought to use different molecular surfaces to mediate the protein-protein interactions required for their otherwise similar functions. This genetically separable function suggests convergent evolution of primate lentiviruses and/or structural differences between human and nonhuman primate cellular target proteins. However, such comparative molecular analyses have not been undertaken so far using the respective natural host-derived cellular targets. We cloned simian Src family kinase Hck and analyzed structurally and biochemically its interaction with SIV Nef.