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July 2018 Research Update

Closer to a Cure? Elucidating the Structure of the HIV Reverse Transcriptase Initiation Complex

Last month, in a study published in Nature, a team of researchers from Stanford University unraveled the structural basis of the HIV reverse transcriptase initiation complex (RTIC), the discovery of which may have brought us closer to a cure for HIV.

Although the structure of each HIV component has previously been elucidated, the structural basis of the initiation of transcription has remained elusive despite lasting efforts to uncover it.

Understanding this process provides new opportunities for drug targeting, which could be essential for maintaining control of the rapidly mutating virus.

"A rich body of structural data on reverse transcriptase (RT), a heterodimer of p51 and p66 sub-units, has shown how its polymerase and RNase H domains interact with DNA-DNA and DNA-RNA duplexes in the absence and presence of antiviral drugs. Lacking, however, are structures that reflect initiation, showing how RT binds to a large bimolecular viral RNA(vRNA)-tRNALys complex," the authors explain.

Using a combination of cryo-electron microscopy, biochemical, and biophysical experiments, this group of researchers built an RTIC model. In this model, the RT is in an inactive conformation with open fingers and thumb, while the primer-template complex is turned away from...

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Zone In With The Zon Blog Post

ATP Synthase and ATPase: In Memory of Paul D. Boyer and Jens C. Skou

• ATP Is the "Molecular Unit of Currency" of Intracellular Energy Transfer

• 1997 Nobelists Boyer and Skou Elucidated Fundamental ATP Biochemistry

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