Disease relevance of Penton

• The fibers are released, the penton base structures dissociated, the proteins connecting the DNA to the inside surface of the capsid degraded or shed, and the capsid-stabilizing minor proteins eliminated [1].
• The adenovirus penton, a noncovalent complex of the pentameric penton base and trimeric fiber proteins, comprises the vertices of the adenovirus capsid and contains all necessary components for viral attachment and internalization [2].
• The structure of the human adenovirus 2 penton [2].
• Data from specific ligand elution of phages bound to fiber and penton base wild-types and mutants suggested that the region overlapping the RLSNLLG motif at residues 254-260 in the penton base and the FNPVYP motif at residues 11-16 in the fiber tail formed mutual interacting sites in the penton capsomer [3].
• It was recently shown that co-expression of adenovirus type 3 (Ad3) penton base and fibre in the baculovirus system produces dodecahedral particles, as does the expression of the penton base alone [4].

High impact information on Penton

• We demonstrate that the vitro-nectin-binding integrins alpha v beta 3 and alpha v beta 5 promote viral infection in a novel way since antibodies against these receptors or soluble penton base block virus internalization without affecting attachment [5].
• Human adenovirus type 2 (Ad2) enters host cells by receptor-mediated endocytosis, an event mediated by the virus penton base binding to cell surface integrins alpha v beta 3 and alpha v beta 5 [6].
• When this region of the penton was mutated, TNF-alpha expression and bone marrow-derived DC maturation were attenuated [7].
• The adenovirus capsid protein penton contains a well characterized arginine-glycine-aspartic acid integrin-binding domain that stimulates PI3K in fibroblast cell lines [7].
• Furthermore, this property of CAR does not require its cytoplasmic domain, consistent with the idea that CAR primarily serves as a high affinity binding site for the adenoviral fiber protein, and that viral entry is mediated by interaction of the viral penton base proteins with cellular integrins [8].

Chemical compound and disease context of Penton

• 100K of adenovirus 2 wild type (WT) was found to bind in significant amounts to novobiocin-affinity column, and to be coeluted with hexon, penton, IIIa, and cellular topoisomerase II activity, by novobiocin- or ATP-Mg2+-containing buffers [9].
• Two of them (1D2 and 5A5), raised against Ad5 virion as the immunogen, bound to sodium dodecyl sulfate (SDS)-resistant and subgenus C-specific epitopes that were not present in subgenus B Ad3 penton base [10].
• Latex particles, coated with purified hexon, penton or fibre antigens displayed specific agglutination with 21 rabbit immune sera directed against the different antigens and the complete virus of 10 human and 2 animal adenovirus types [11].

Biological context of Penton

• It includes three major open translational reading frames encoding the carboxyl-terminal part of the penton base as well as the major core polypeptides V and VII [12].
• The difference in fiber length may explain the different binding characteristics and tissue tropisms of each virus despite both utilizing the same fiber and penton base receptors [13].
• This complex, which is analogous to that of adenovirus, is formed of the penton protein P31, the spike protein P5, and the receptor binding protein P2 [14].
• The nucleotide sequence encoding the penton base integrin-binding domains of several human adenoviruses was obtained by homology PCR [15].
• This cleavage effect, which did not seem to be related to penton base-associated endonuclease activity, was also enhanced when early gene expression was allowed at 33 degrees C before shift-up [16].

Anatomical context of Penton

• We were able to isolate viral fiber and penton from Ad3-infected KB cells using for their detection antibodies obtained against recombinant Ad3 fiber [17].
• It was shown that penton potentiated the cytotoxicity of gelonin for HeLa cells and that hexon and fiber had no measurable effect on the cytotoxicity of gelonin [18].
• The ability to lyse the cellular endosome encapsulating internalized receptors is also attributed to the penton [19].
• Here we investigated the role of the Ad5 surface domain proteins constituting the vector capsid, namely, the fiber, the penton base, and the hexon, on the transmembrane signals leading to the transcription of the different proinflammatory genes in the human respiratory A549 cell line [20].
• An interaction between penton base and alpha v integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo [21].

Associations of Penton with other chemical compounds

• 0. Among the three major external proteins (hexon, penton base, and fiber), penton base had the highest association with Triton X-114 at pH 5 [22].
• Assessment of cell surface expression of Ad receptors demonstrated that both the high-affinity coxsackie-adenovirus receptor for Ad fiber protein and the low-affinity alpha(v) integrin receptor for Ad penton base protein showed increased cell surface expression at M phase (1.5-fold and 2- to 3-fold increases, respectively) [23].
• Conserved within this variable region is the sequence Arg-Gly-Asp (RGD), which, in the Ad2 penton base, binds to integrins in the target cell membrane, enhancing the rate or the efficiency of infection [24].

Gene context of Penton

• These regions contain the coding sequences for the 52,55K polypeptide, polypeptide IIIa, penton base, and the N terminus of the 100K polypeptide [25].
• Our data suggested that GRP receptors could function efficiently as alternative attachment receptors for Ad5, but virus bound to GRP receptors still depended partially on the penton base-mediated pathway for cell entry [26].
• Interaction of Ad fiber with CAR activates both ERK1/2 and JNK MAPK and the nuclear translocation of NF-kappaB, whereas no activation was observed after exposing A549 cells to penton base and hexon proteins [20].
• By immunoprecipitating protein products from virus-infected baby rat kidney (BRK) cells with specific antibodies, we found that the smaller, 243 residue (243R) E1A protein of human adenovirus 5 (Ad5) activated expression of the virus genes for E1B 55K, E2A 72K, E3 19K, hexon, fibre and penton base and the cellular gene for PCNA [27].
• The protein crystals, which result from the regular assembly of hexon, penton base, and fiber proteins [Boulanger et al. (1970) J Gen Virol 6:329-332], contained CK2 beta and PKR [28].

Analytical, diagnostic and therapeutic context of Penton

• We propose the use of a dodecahedron made of adenovirus pentons or penton bases as an alternative vector for human gene therapy [29].
• The titre and isotype of anti-adenovirus antibodies was determined by ELISA, and Western blotting identified the molecular basis of the immune response, which was primarily directed towards fibre and penton base [30].
• Depletion of antibodies to individual adenovirus structural proteins (hexon, penton, fiber) by affinity chromatography demonstrated that antibodies to each of the three virion components contributed to neutralization of infectivity in vitro and to inhibition of transduction in vivo [31].
• Presence of viral protein at both 37 h and 7 days was confirmed by immunohistochemistry using antibodies directed against hexon, penton, and fiber proteins [32].
• Structure determination of the fiberless dodecahedron by cryo-electron microscopy to 9 Angstroms resolution reveals tightly bound pentamer subunits, with only minimal interfaces between penton bases stabilizing the fragile dodecahedron [33].

References