| Structural highlights
Function
[CAP6_ADE05] Pre-protein VI: During virus assembly, promotes hexon trimers nuclear import through nuclear pore complexes via an importin alpha/beta-dependent mechanism. By analogy to herpesviruses capsid assembly, might act as a scaffold protein to promote the formation of the icosahedral capsid.[1] [2] [3] [4] [5] Endosome lysis protein: Structural component of the virion that provides increased stability to the particle shell through its interaction with the core-capsid bridging protein. Fibers shedding during virus entry into host cell allows the endosome lysis protein to be exposed as a membrane-lytic peptide. Exhibits pH-independent membrane fragmentation activity and probably mediates viral rapid escape from host endosome via organellar membrane lysis. It is not clear if it then remains partially associated with the capsid and involved in the intracellular microtubule-dependent transport of capsid to the nucleus, or if it is lost during endosomal penetration.[6] [7] [8] [9] [10] Protease cofactor: Cofactor that activates the viral protease. Binds to viral protease in a 1:1 ratio.[11] [12] [13] [14] [15] [CAP9_ADE05] Structural component of the virion that presumably stabilizes the groups of hexons but is dispensable for assembly. During virus entry, recruits the anterograde motor kinesin-1 to the capsid docked at the nuclear pore complex thereby subjecting the docked capsid to a pulling force. The resulting tension leads to capsid disruption, dispersion of capsid fragments toward cell periphery and eventually viral DNA entry into the host nucleus. [CAPSH_ADE05] Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chaperone shutoff protein (By similarity). Transported by pre-protein VI to the nucleus where it associates with other structural proteins to form an empty capsid. Might be involved, through its interaction with host dyneins, in the intracellular microtubule-dependent transport of incoming viral capsid to the nucleus. [CAP3_ADE05] Structural component of the virion that is likely to participate in vertex stabilization and genome packaging. Stabilizes vertices by tethering the penton bases to neighboring peripentonal hexons. Lashes peripentonal hexons to the neighboring hexons thanks to its interaction with hexon-linking protein. As the virus enters the host cell, capsid vertex proteins are shed concomitant with virion acidification in the endosome. During virus assembly, seems to play a role in packaging of viral DNA via its interaction with packaging protein 3.[16] [17] [CAPSP_ADE05] Major capsid protein that self-associates to form penton base pentamers, each in the shape of a pentagon, situated at the 12 vertices of the pseudo T=25 capsid. Involved in virus secondary attachment to host cell after initial attachment by the fiber protein. Binds host integrin heterodimer ITGAV-ITGB5 (alphaV-beta5) thereby triggering clathrin-mediated endocytosis of virions. Mediates initial virus attachment to CXADR-negative cells. Binding to integrins ITGAV-ITGB5 also seems to induce macropinocytosis uptake of the virus. As the virus enters the host cell, penton proteins are shed concomitant with virion acidification in the endosome.[18] [19] [CAP8_ADE05] Hexon-linking protein: Structural component of the virion that lashes peripentonal hexons to the hexons situated in the facets thanks to its interaction with the capsid vertex protein. Also binds together hexons of different facets.
Publication Abstract from PubMed
Human adenoviruses (HAdVs) cause acute respiratory, ocular, and gastroenteric diseases and are also frequently used as gene and vaccine delivery vectors. Unlike the archetype human adenovirus C5 (HAdV-C5), human adenovirus D26 (HAdV-D26) belongs to species-D HAdVs, which target different cellular receptors, and is differentially recognized by immune surveillance mechanisms. HAdV-D26 is being championed as a lower seroprevalent vaccine and oncolytic vector in preclinical and human clinical studies. To understand the molecular basis for their distinct biological properties and independently validate the structures of minor proteins, we determined the first structure of species-D HAdV at 3.7 A resolution by cryo-electron microscopy. All the hexon hypervariable regions (HVRs), including HVR1, have been identified and exhibit a distinct organization compared to those of HAdV-C5. Despite the differences in the arrangement of helices in the coiled-coil structures, protein IX molecules form a continuous hexagonal network on the capsid exterior. In addition to the structurally conserved region (3 to 300) of IIIa, we identified an extra helical domain comprising residues 314 to 390 that further stabilizes the vertex region. Multiple (two to three) copies of the cleaved amino-terminal fragment of protein VI (pVIn) are observed in each hexon cavity, suggesting that there could be >/=480 copies of VI present in HAdV-D26. In addition, a localized asymmetric reconstruction of the vertex region provides new details of the three-pronged "claw hold" of the trimeric fiber and its interactions with the penton base. These observations resolve the previous conflicting assignments of the minor proteins and suggest the likely conservation of their organization across different HAdVs.
Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses.,Yu X, Veesler D, Campbell MG, Barry ME, Asturias FJ, Barry MA, Reddy VS Sci Adv. 2017 May 10;3(5):e1602670. doi: 10.1126/sciadv.1602670. eCollection 2017, May. PMID:28508067[20]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wodrich H, Guan T, Cingolani G, Von Seggern D, Nemerow G, Gerace L. Switch from capsid protein import to adenovirus assembly by cleavage of nuclear transport signals. EMBO J. 2003 Dec 1;22(23):6245-55. PMID:14633984 doi:http://dx.doi.org/10.1093/emboj/cdg614
- ↑ Wiethoff CM, Wodrich H, Gerace L, Nemerow GR. Adenovirus protein VI mediates membrane disruption following capsid disassembly. J Virol. 2005 Feb;79(4):1992-2000. PMID:15681401 doi:http://dx.doi.org/10.1128/JVI.79.4.1992-2000.2005
- ↑ Wodrich H, Henaff D, Jammart B, Segura-Morales C, Seelmeir S, Coux O, Ruzsics Z, Wiethoff CM, Kremer EJ. A capsid-encoded PPxY-motif facilitates adenovirus entry. PLoS Pathog. 2010 Mar 19;6(3):e1000808. doi: 10.1371/journal.ppat.1000808. PMID:20333243 doi:http://dx.doi.org/10.1371/journal.ppat.1000808
- ↑ Maier O, Galan DL, Wodrich H, Wiethoff CM. An N-terminal domain of adenovirus protein VI fragments membranes by inducing positive membrane curvature. Virology. 2010 Jun 20;402(1):11-9. doi: 10.1016/j.virol.2010.03.043. Epub 2010, Apr 20. PMID:20409568 doi:http://dx.doi.org/10.1016/j.virol.2010.03.043
- ↑ Moyer CL, Wiethoff CM, Maier O, Smith JG, Nemerow GR. Functional genetic and biophysical analyses of membrane disruption by human adenovirus. J Virol. 2011 Mar;85(6):2631-41. doi: 10.1128/JVI.02321-10. Epub 2011 Jan 5. PMID:21209115 doi:http://dx.doi.org/10.1128/JVI.02321-10
- ↑ Wodrich H, Guan T, Cingolani G, Von Seggern D, Nemerow G, Gerace L. Switch from capsid protein import to adenovirus assembly by cleavage of nuclear transport signals. EMBO J. 2003 Dec 1;22(23):6245-55. PMID:14633984 doi:http://dx.doi.org/10.1093/emboj/cdg614
- ↑ Wiethoff CM, Wodrich H, Gerace L, Nemerow GR. Adenovirus protein VI mediates membrane disruption following capsid disassembly. J Virol. 2005 Feb;79(4):1992-2000. PMID:15681401 doi:http://dx.doi.org/10.1128/JVI.79.4.1992-2000.2005
- ↑ Wodrich H, Henaff D, Jammart B, Segura-Morales C, Seelmeir S, Coux O, Ruzsics Z, Wiethoff CM, Kremer EJ. A capsid-encoded PPxY-motif facilitates adenovirus entry. PLoS Pathog. 2010 Mar 19;6(3):e1000808. doi: 10.1371/journal.ppat.1000808. PMID:20333243 doi:http://dx.doi.org/10.1371/journal.ppat.1000808
- ↑ Maier O, Galan DL, Wodrich H, Wiethoff CM. An N-terminal domain of adenovirus protein VI fragments membranes by inducing positive membrane curvature. Virology. 2010 Jun 20;402(1):11-9. doi: 10.1016/j.virol.2010.03.043. Epub 2010, Apr 20. PMID:20409568 doi:http://dx.doi.org/10.1016/j.virol.2010.03.043
- ↑ Moyer CL, Wiethoff CM, Maier O, Smith JG, Nemerow GR. Functional genetic and biophysical analyses of membrane disruption by human adenovirus. J Virol. 2011 Mar;85(6):2631-41. doi: 10.1128/JVI.02321-10. Epub 2011 Jan 5. PMID:21209115 doi:http://dx.doi.org/10.1128/JVI.02321-10
- ↑ Wodrich H, Guan T, Cingolani G, Von Seggern D, Nemerow G, Gerace L. Switch from capsid protein import to adenovirus assembly by cleavage of nuclear transport signals. EMBO J. 2003 Dec 1;22(23):6245-55. PMID:14633984 doi:http://dx.doi.org/10.1093/emboj/cdg614
- ↑ Wiethoff CM, Wodrich H, Gerace L, Nemerow GR. Adenovirus protein VI mediates membrane disruption following capsid disassembly. J Virol. 2005 Feb;79(4):1992-2000. PMID:15681401 doi:http://dx.doi.org/10.1128/JVI.79.4.1992-2000.2005
- ↑ Wodrich H, Henaff D, Jammart B, Segura-Morales C, Seelmeir S, Coux O, Ruzsics Z, Wiethoff CM, Kremer EJ. A capsid-encoded PPxY-motif facilitates adenovirus entry. PLoS Pathog. 2010 Mar 19;6(3):e1000808. doi: 10.1371/journal.ppat.1000808. PMID:20333243 doi:http://dx.doi.org/10.1371/journal.ppat.1000808
- ↑ Maier O, Galan DL, Wodrich H, Wiethoff CM. An N-terminal domain of adenovirus protein VI fragments membranes by inducing positive membrane curvature. Virology. 2010 Jun 20;402(1):11-9. doi: 10.1016/j.virol.2010.03.043. Epub 2010, Apr 20. PMID:20409568 doi:http://dx.doi.org/10.1016/j.virol.2010.03.043
- ↑ Moyer CL, Wiethoff CM, Maier O, Smith JG, Nemerow GR. Functional genetic and biophysical analyses of membrane disruption by human adenovirus. J Virol. 2011 Mar;85(6):2631-41. doi: 10.1128/JVI.02321-10. Epub 2011 Jan 5. PMID:21209115 doi:http://dx.doi.org/10.1128/JVI.02321-10
- ↑ Ma HC, Hearing P. Adenovirus structural protein IIIa is involved in the serotype specificity of viral DNA packaging. J Virol. 2011 Aug;85(15):7849-55. doi: 10.1128/JVI.00467-11. Epub 2011 Jun 1. PMID:21632753 doi:http://dx.doi.org/10.1128/JVI.00467-11
- ↑ Liu H, Jin L, Koh SB, Atanasov I, Schein S, Wu L, Zhou ZH. Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science. 2010 Aug 27;329(5995):1038-43. PMID:20798312 doi:10.1126/science.1187433
- ↑ Lyle C, McCormick F. Integrin alphavbeta5 is a primary receptor for adenovirus in CAR-negative cells. Virol J. 2010 Jul 8;7:148. doi: 10.1186/1743-422X-7-148. PMID:20615244 doi:10.1186/1743-422X-7-148
- ↑ Liu H, Jin L, Koh SB, Atanasov I, Schein S, Wu L, Zhou ZH. Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science. 2010 Aug 27;329(5995):1038-43. PMID:20798312 doi:10.1126/science.1187433
- ↑ Yu X, Veesler D, Campbell MG, Barry ME, Asturias FJ, Barry MA, Reddy VS. Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses. Sci Adv. 2017 May 10;3(5):e1602670. doi: 10.1126/sciadv.1602670. eCollection 2017, May. PMID:28508067 doi:http://dx.doi.org/10.1126/sciadv.1602670
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