2JYS

Solution structure of Simian Foamy Virus (mac) protease

Summary for 2JYS

• Entry DOI: 10.2210/pdb2jys/pdb
• Descriptor: Protease/Reverse transcriptase (1 entity in total)
• Functional Keywords: retroviral protease, hydrolase
• Biological source: Simian foamy virus type 1 (SFVmac)
• Cellular location: Integrase: Virion (Potential). Protease/Reverse transcriptase/ribonuclease H: Host nucleus (By similarity): P23074
• Total number of polymer chains: 1
• Total formula weight: 12409.32

Authors

Hartl, M.J.,Woehrl, B.M.,Roesch, P.,Schweimer, K. (deposition date: 2007-12-19, release date: 2008-06-03, Last modification date: 2024-05-29)

Primary citation

Hartl, M.J.,Woehrl, B.M.,Roesch, P.,Schweimer, K.
The solution structure of the simian foamy virus protease reveals a monomeric protein
J.Mol.Biol., 381:141-149, 2008

PubMed Abstract: In contrast to orthoretroviruses, foamy viruses (FVs) express their Pol polyprotein from a separate pol-specific transcript. Only the integrase domain is cleaved off, leading to a protease-reverse transcriptase (PR-RT) protein. We purified the separate PR domain (PRshort) of simian FV from macaques by expressing the recombinant gene in Escherichia coli. Sedimentation analyses and size exclusion chromatography indicate that PRshort is a stable monomer in solution. This allowed us to determine the structure of the PRshort monomer using 1426 experimental restraints derived from NMR spectroscopy. The superposition of 20 conformers resulted in a backbone atom rmsd of 0.55 A for residues Gln8-Leu93. Although the overall folds are similar, the macaque simian FV PRshort reveals significant differences in the dimerization interface relative to other retroviral PRs, such as HIV-1 (human immunodeficiency virus type 1) PR, which appear to be rather stable dimers. Especially the flap region and the N- and C-termini of PRshort are highly flexible. Neglecting these regions, the backbone atom rmsd drops to 0.32 A, highlighting the good definition of the central part of the protein. To exclude that the monomeric state of PRshort is due to cleaving off the RT, we purified the complete PR-RT and performed size exclusion chromatography. Our data show that PR-RT is also monomeric. We thus conclude adoption of a monomeric state of PR-RT to be a regulatory mechanism to inhibit PR activity before virus assembly in order to reduce packaging problems. Dimerization might therefore be triggered by additional viral or cellular factors.

PubMed: 18597783
DOI: 10.1016/j.jmb.2008.05.064

Experimental method

SOLUTION NMR