9tx9 | pdb_00009tx9
Mature MPMV E26A capsid hexamer structure from capsid-like particles
Structural highlights
FunctionPOL_MPMV Matrix protein p10: Matrix protein. Nucleocapsid protein p14: Nucleocapsid protein. Capsid protein p27: Capsid protein. Protease 17 kDa: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell.[PROSITE-ProRule:PRU00275][1] Protease 13 kDa: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell.[PROSITE-ProRule:PRU00275][2] G-patch peptide: Enhances the activity of the reverse transcriptase. May be part of the mature RT.[3] Reverse transcriptase/ribonuclease H: RT is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5' end of the viral RNA. RT uses the 3' end of the tRNA primer to perfom a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perfom the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5' end of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primers. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.[PROSITE-ProRule:PRU00405] Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions.[4] Publication Abstract from PubMedHIV-1 uses the metabolite inositol hexakisphosphate (IP(6)) as a host factor to assemble its capsid, but whether this strategy is unique to lentiviruses or represents a common feature of retroviral capsids remains unclear. Here we show that IP(6) binding is conserved across diverse retroviruses but occurs through distinct capsid sites and mechanisms, and influences viral behaviour. In contrast to HIV-1, the beta-retrovirus Mason-Pfizer Monkey Virus (MPMV) and the gamma-retrovirus Murine Leukaemia Virus (MLV) bind IP(6) at the threefold lattice interface between capsomers rather than within capsomer pores. Cryo-EM structures of core-like particles reveal that two lysine residues from each capsomer coordinate IP(6) between either two discrete three-lysine rings (MPMV) or a single heterogeneous six-lysine ring (MLV). MPMV and MLV are largely insensitive to IP(6) availability in producer cells, but this binding mode renders them highly dependent on IP6 in target cells - the opposite of the dependency pattern of HIV-1. The way in which retroviruses use IP(6) to build their capsids alters their dependence on the metabolite at different stages of the replicative cycle and in key capsid behaviours, such as assembly and stability. Retroviruses use different IP(6) binding mechanisms to alter the properties of their capsids.,Klarhof JO, Mallery DL, Stacey JCV, Torre D, Rumlova M, Ruml T, Briggs JAG, James LC Nat Commun. 2026 Aug 21;17(1):10005. doi: 10.1038/s41467-026-76510-7. PMID:42764334[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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