{
  "abstract": "The AAV2 capsid assembles from three viral proteins, VP1, VP2, and VP3, expressed from a single cap gene. In the assembled T=1 60-subunit icosahedral capsid, they have a canonical stoichiometry of 1:1:10. Relative to VP3, VP1 and VP2 have N-terminal extensions that are required for endosomal escape and nuclear trafficking; however, these regions remain poorly resolved due to low stoichiometry, symmetry mismatches, and conformational heterogeneity of their N-termini. Here, we generated empty AAV2 capsids using a baculovirus expression system with time-course harvests, yielding approximately 2:3:5 and 1:2:7. VP1:VP2:VP3 ratios on days 3 and 5 post-infection, respectively. Cryo-EM single-particle and subparticle reconstructions revealed distinct N-terminal configurations associated with these different VP stoichiometries. Day 3 capsids contained an internal density protruding from the twofold axis and lacked the ordered {beta}A preceding residue 237, whereas day 5 capsids lacked the twofold protrusion and instead showed density associated with the fivefold axis, with {beta}A ordered to approximately residues 219-221. Fivefold subparticle reconstruction of day 5 capsids further resolved a density plug occluding the pore and an underlying density ring. These findings link VP stoichiometry to distinct conformations of the VP1/VP2 N-termini and provide structural evidence for alternative organization of these regions within the AAV2 capsid, offering new insights into the conformational landscape of AAV capsid heterogeneity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biological Science, Florida State University, Tallahassee, Florida, USA., Institute of Molecular Biophysics, Florida State University, Tallahassee"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "I. O. Osuya"
    },
    {
      "name": "S. S. Kamalaldinezabadi"
    },
    {
      "name": "A. Sengupta"
    },
    {
      "name": "G. Seo"
    },
    {
      "name": "M. S. Chapman"
    },
    {
      "affs": [
        0
      ],
      "name": "S. M. Stagg"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3yapd8h8811m1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.759763",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759763v1.full",
  "id": "3yapd8h8811m1",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759763v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7222885903",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759763v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3yapd8h8811m1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:20Z",
      "native_id": "10.64898/2026.10.16.759763",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759763v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Cryo-EM Reveals VP1/VP2 N-Terminal Conformations in Adeno-Associated Virus 2 Capsids.",
  "title_text": "Cryo-EM Reveals VP1/VP2 N-Terminal Conformations in Adeno-Associated Virus 2 Capsids.",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:20Z",
  "url": "https://research.draconitic.com/paper/3yapd8h8811m1",
  "venue": "bioRxiv",
  "versions": []
}