High-resolution structure of a retroviral protease folded as a monomer

摘要: Mason–Pfizer monkey virus (M-PMV), a D-type retrovirus assembling in the cytoplasm, causes simian acquired immuno­deficiency syndrome (SAIDS) rhesus monkeys. Its pepsin-like aspartic protease (retropepsin) is an integral part of expressed retroviral polyproteins. As all life cycles, release and dimerization (PR) strictly required for polyprotein processing virion maturation. Biophysical NMR studies have indicated that absence substrates or inhibitors M-PMV PR should fold into stable monomer, but crystal structure this protein could not be solved by molecular replacement despite countless attempts. Ultimately, solution was obtained mr-rosetta using model constructed players online protein-folding game Foldit. The indeed shows monomeric protein, with N- C-termini completely disordered. On other hand, flap loop, which normally gates access to active site homodimeric retropepsins, is clearly traceable electron density. has unusual curled shape different orientation from both open closed states known dimeric retropepsins. overall follows retropepsin canon, Cα deviations are large active-site `DTG' loop (here NTG) deviates up 2.7 A standard con­formation. This determined at high resolution (1.6 A) provides important extra information design might developed as drugs treatment infections, including AIDS.