9swa

Adenovirus dodecahedron

spinqualitylabelsall models 9swa, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9swa is a 60 chain structure with sequence from Chimpanzee adenovirus Y25. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.2Å Ligands: K Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G9G849_9ADEN 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, and in endocytosis of virions. As the virus enters the host cell, penton proteins are shed concomitant with virion acidification in the endosome.[HAMAP-Rule:MF_04052] Publication Abstract from PubMed Virus-like particles (VLPs) are promising platforms for next-generation vaccines due to their ability to present antigens in highly ordered, repetitive geometries emulating pathogen-associated patterns to elicit potent immune responses. The ADDomer is a synthetic dodecahedral VLP scaffold derived from the penton base protein (PBP) of human adenovirus serotype 3 (Ad3). PBP tolerates insertion of multiple antigenic epitopes in flexible surface-exposed loops, and spontaneously self-assembles in vitro into ADDomer nanoparticles, but faces limitations including incomplete assembly and susceptibility to preexisting antihuman adenovirus immunity. Here, we report two complementary engineering strategies to enhance ADDomer robustness. First, we developed a Chimpanzee adenovirus Y25-based ADDomer (CHIMPSELS) to circumvent preexisting antihuman adenovirus immunity, and introduced a point mutation to restore a motif critical for dodecahedron integrity. Second, we introduced targeted intersubunit disulfide bonds to reinforce particle assembly. High-resolution electron cryo-microscopy confirmed the formation of intact dodecahedral particles, revealing that disulfide bonds stabilize distinct conformations of the PBP N-termini. Differential scanning fluorimetry and dynamic light scattering demonstrated thermal stability and elevated aggregation onset temperatures in the disulfide-stabilized ADDomers, providing a scalable assay for screening ADDomer-based VLP constructs for vaccine development. Incorporation of validated immunogenic epitopes, including a SARS-CoV-2 receptor-binding motif segment and the Chikungunya E2EP3 peptide, demonstrated structural integrity and epitope display by the modified scaffolds. Our results establish a versatile, thermostable VLP platform with reduced susceptibility to preexisting immunity, improved particle integrity, and capacity for modular epitope presentation. This work advances the ADDomer toward practical applications in vaccine development and highlights engineering strategies that can be broadly applied to enhance the performance of protein-based VLP vaccines. Engineering the ADDomer Nanoparticle Vaccine Scaffold for Improved Assembly and Enhanced Stability.,Balchin G, Kabasakal BV, Strofaldi A, Hall S, Fletcher C, Buzas D, Bufton JC, Yadav SKN, Shen D, Garzoni F, Bunzel HA, McManus JJ, Schaffitzel C, Berger I ACS Synth Biol. 2026 Mar 16. doi: 10.1021/acssynbio.5c00757. PMID:41840818 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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