Conformational Changes in HIV-1 Gag Regulate its Assembly and Genome Selection

Abstract

Retroviral Gag proteins assemble into virus like particles (VLPs) and package their single stranded RNA genomes (gRNAs). In the majority of cases this assembly happens on the plasma membrane of the cell (PM). In the assembled immature VLP the cationic C-terminal domain of Gag called Nucleocapsid (NC) protein is bound to RNA, while its cationic N-terminal domain called matric (MA) is bound to anionic PM. In this state the Gag protein is extended, i.e. is in its straight conformation that is able to assemble. However, the Gag polyprotein has several flexible hinges between its domains, and is bent is solution. Gag is also in its bent and non-assembling state when bound to RNA or to PM with its both cationic domains NC and MA. In this work we present statistical description of the conformational transition in Gag that leads to its assembly initiation. We discuss implications of the Gag bent to straight conformational transition for genomic RNA selection.