Structural basis of microtubule depolymerization by the kinesin-like activity of HIV-1 Rev.

ABSTRACT

HIV-1 Rev is an essential regulatory protein that transports unspliced and partially spliced viral mRNAs from the nucleus to the cytoplasm for the expression of viral structural proteins. During its nucleocytoplasmic shuttling, Rev interacts with several host proteins to use the cellular machinery for the advantage of the virus. Here, we report the 3.5 Å cryo-EM structure of a 4.8 MDa Rev-tubulin ring complex. Our structure shows that Rev's arginine-rich motif (ARM) binds to both the acidic surfaces and the C-terminal tails of α/ß-tubulin. The Rev-tubulin interaction is functionally homologous to that of kinesin-13, potently destabilizing microtubules at sub-stoichiometric levels. Expression of Rev in astrocytes and HeLa cells shows that it can modulate the microtubule cytoskeleton within the cellular environment. These results show a previously undefined regulatory role of Rev.