The role of the S-S bridge in retroviral protease function and virion maturation
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
17140600
DOI
10.1016/j.jmb.2006.11.005
PII: S0022-2836(06)01534-8
Knihovny.cz E-zdroje
- MeSH
- bromkyan metabolismus MeSH
- Cercopithecus aethiops MeSH
- COS buňky MeSH
- cystein metabolismus MeSH
- dimerizace MeSH
- disulfidy metabolismus MeSH
- endopeptidasy chemie metabolismus ultrastruktura MeSH
- fluorescenční spektrometrie MeSH
- genové produkty gag metabolismus MeSH
- kinetika MeSH
- Masonův-Pfizerův opičí virus enzymologie fyziologie MeSH
- molekulární sekvence - údaje MeSH
- molekulová hmotnost MeSH
- mutantní proteiny chemie metabolismus MeSH
- nukleární magnetická rezonance biomolekulární MeSH
- posttranslační úpravy proteinů MeSH
- replikace viru fyziologie MeSH
- retrovirové infekce MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- stabilita enzymů MeSH
- termodynamika MeSH
- virion fyziologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bromkyan MeSH
- cystein MeSH
- disulfidy MeSH
- endopeptidasy MeSH
- genové produkty gag MeSH
- Mason-Pfizer monkey virus protease MeSH Prohlížeč
- mutantní proteiny MeSH
Retroviral proteases are translated as a part of Gag-related polyproteins, and are released and activated during particle release. Mason-Pfizer monkey virus (M-PMV) Gag polyproteins assemble into immature capsids within the cytoplasm of the host cells; however, their processing occurs only after transport to the plasma membrane and subsequent release. Thus, the activity of M-PMV protease is expected to be highly regulated during the replication cycle. It has been proposed that reversible oxidation of protease cysteine residues might be responsible for such regulation. We show that cysteine residues in M-PMV protease can form an intramolecular S-S bridge. The disulfide bridge shifts the monomer/dimer equilibrium in favor of the dimer, and increases the proteolytic activity significantly. To investigate the role of this disulfide bridge in virus maturation and replication, we engineered an M-PMV clone in which both protease cysteine residues were replaced by alanine (M-PMV(PRC7A/C106A)). Surprisingly, the cysteine residues were dispensable for Gag polyprotein processing within the virus, indicating that even low levels of protease activity are sufficient for polyprotein processing during maturation. However, the long-term infectivity of M-PMV(PRC7A/C106A) was noticeably compromised. These results show clearly that the proposed redox mechanism does not rely solely on the formation of the stabilizing S-S bridge in the protease. Thus, in addition to the protease disulfide bridge, reversible oxidation of cysteine and/or methionine residues in other domains of the Gag polyprotein or in related cellular proteins must be involved in the regulation of maturation.
Citace poskytuje Crossref.org
Crystal structures of inhibitor complexes of M-PMV protease with visible flap loops
The G-patch domain of Mason-Pfizer monkey virus is a part of reverse transcriptase
