RNA-directed remodeling of the HIV-1 protein Rev orchestrates assembly of the Rev–Rev response element complex

摘要

To be able to multiply, viruses have to first infect a host cell and then hijack the host's molecular machinery to make viral proteins. One stage of this process takes place in the nucleus of the host cell and involves the viral DNA being transcribed to make RNA molecules. These RNA molecules must then be exported from the nucleus to the cytoplasm, where the viral proteins are made. In the case of HIV-1, a protein called Rev has an important role in the export process. The Rev protein, which is supplied by the virus, binds to a region on the viral RNA molecules called the Rev Response Element. The Rev protein then binds to a group of host proteins called the Crm1 export complex to send the viral RNA molecules to the cytoplasm. Jayaraman et al. now provide the first in-depth 3D structure of two Rev molecules bound to a fragment of the Rev Response Element. The Rev molecules change shape when they bind to the element, and specific regions of the element were found to be important for this. The experiments suggest that the Rev Response Element directs the positioning of the Rev proteins on itself to match the shape needed to bind to Crm1 export complex. In parallel work from the same laboratory, Booth et al. have produced a 3D structure of the whole complex. Both structures shed new light on how the HIV-1 virus is able to multiply in its host, which may aid future efforts to develop new treatments for the disease.