6cgv
From Proteopedia
Revised crystal structure of human adenovirus
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 PubMedWe report the revised crystal structure of a pseudo-typed human adenovirus at 3.8-A resolution that is consistent with the atomic models of minor proteins determined by cryo-electron microscopy. The diffraction data from multiple crystals were rescaled and merged to increase the data completeness. The densities for the minor proteins were initially identified in the phase-refined omit maps that were further improved by the phases from docked poly-alanine models to build atomic structures. While the trimeric fiber molecules are disordered due to flexibility and imposition of 5-fold symmetry, the remaining major capsid proteins hexon and penton base are clearly ordered, with the exception of hypervariable region 1 of hexons, the RGD containing loop, and the N-termini of the penton base. The exterior minor protein IX together with the interior minor proteins IIIa and VIII stabilizes the adenovirus virion. A segment of N-terminal pro-peptide of VI is found in the interior cavities of peripentonal hexons, and the rest of VI is disordered. While the triskelion substructures formed by the N-termini of IX conform to excellent quasi 3-fold symmetry, the tetrameric coiled-coils formed by the C-termini and organized in parallel and anti-parallel arrangement do not exhibit any quasi-symmetry. This observation also conveys the pitfalls of using the quasi-equivalence as validation criteria for the structural analysis of extended (non-modular) capsid proteins such as IX. Together, these results remedy certain discrepancies in the previous X-ray model in agreement with the cryo-electron microscopy models. Revised Crystal Structure of Human Adenovirus Reveals the Limits on Protein IX Quasi-Equivalence and on Analyzing Large Macromolecular Complexes.,Kundhavai Natchiar S, Venkataraman S, Mullen TM, Nemerow GR, Reddy VS J Mol Biol. 2018 Aug 17. pii: S0022-2836(18)30639-9. doi:, 10.1016/j.jmb.2018.08.011. PMID:30121295[20] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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