1.A.53.1.1 Hepatitis C Virus, HCV-P7, of 63 aas and 2 TMSs (Clarke et al., 2006). It's mechanism and function have been investigated in considerable detail (Gan et al. 2014). Histidine-17, which faces the lumen of the pore when protonated, allows Cl- entry, but deprotonation also allows Ca2+ entry. Imposition of voltage creates a Cl- current (Wang et al. 2014). The structure and dual pore/ion channel activity of p7 of different HCV genotypes have been reviewed (Madan and Bartenschlager 2015). It may transport protons (Scott and Griffin 2015); it's structure has been determined by NMR (Montserret et al. 2010) and by electron microscopy (Luik et al. 2009). The p7 N-terminal helical region is critical for
E2/p7 processing, protein-protein interactions, ion channel activity, and infectious HCV production (Scull et al. 2015). HCV p7 is released from the viral polyprotein through cleavage at E2-p7 and p7-NS2 junctions by signal peptidase, but also exists as an E2p7 precursor. The retarded E2p7 precursor cleavage is essential to regulate the intracellular and secreted levels of E2 through p7-mediated modulation of the cell secretory pathway (Denolly et al. 2017). Chen et al. 2018 provided evidence that the oligomeric channel is a cation-selective hexamer. The his-9 in the hexameric model forms a
first gate, acting as a selectivity filter for
cations. while valines form a second gate, serving as a hydrophobic filter for dehydrated cations. The
binding pocket for the channel blockers, amantadine and
rimantadine, is composed of residues 20-26 in H2 helix and 52-60 in H3
helix (Ying et al. 2018). Two of the best inhibitors were ARD87 and ARD112 (Wei et al. 2021).
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Accession Number: | Q5QRI8 |
Protein Name: | P7 aka Polyprotein |
Length: | 63 |
Molecular Weight: | 6778.00 |
Species: | Hepatitis C virus subtype 1b [31647] |
Number of TMSs: | 2 |
Location1 / Topology2 / Orientation3: |
Secreted1 |
Substrate |
chloride, cation, calcium(2+), 17beta-hydroxy-5alpha-androstan-3-one |
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[1] “Hepatitis C Virus p7 membrane protein quasispecies variability in chronically infected patients treated with interferon and ribavirin, with or without amantadine.” Castelain S. et.al. 17177298
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1: ALENLVVLNA ASLAGAHGIL SFLVFFCAAW YIKGRLVPGA AYAFYGVWPL LLLLLTLPPR
61: AYA