Structure of Adeno-Associated Virus Serotype 5
Open accessAbstract
Adeno-associated virus serotype 5 (AAV5) requires sialic acid on host cells to bind and infect. Other parvoviruses, including Aleutian mink disease parvovirus (ADV), canine parvovirus (CPV), minute virus of mice, and bovine parvovirus, also bind sialic acid. Hence, structural homology may explain this functional homology. The amino acids required for CPV sialic acid binding map to a site at the icosahedral twofold axes of the capsid. In contrast to AAV5, AAV2 does not bind sialic acid, but rather binds heparan sulfate proteoglycans at its threefold axes of symmetry. To explore the structure-function relationships among parvoviruses with respect to cell receptor attachment, we determined the structure of AAV5 by cryo-electron microscopy (cryo-EM) and image reconstruction at a resolution of 16 A. Surface features common to some parvoviruses, namely depressions encircling the fivefold axes and protrusions at or surrounding the threefold axes, are preserved in the AAV5 capsid. However, even though there were some similarities, a comparison of the AAV5 structure with those of ADV and CPV failed to reveal a feature which could account for the sialic acid binding phenotype common to all three viruses. In contrast, the overall surface topologies of AAV5 and AAV2 are similar. A pseudo-atomic model generated for AAV5 based on the crystal structure of AAV2 and constrained by the AAV5 cryo-EM envelope revealed differences only in surface loop regions. Surprisingly, the surface topologies…
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Ordered DNA has yet to be discovered in the crystal structures solved for AAV, suggesting that DNA-capsid interactions may be lacking or not as important for AAV.
“However, ordered DNA has yet to be discovered in the crystal structures solved for AAV, suggesting that DNA-capsid interactions may be lacking or not as important for AAV (42, 48).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [42]
The Methods (p. 2) say the AAV5 reconstruction used images of empty capsids, and the Results (p. 3) describe a cryo-EM reconstruction, not an AAV5 crystal structure. Searches for ordered DNA and DNA–capsid interactions found no passage stating whether ordered DNA appears in AAV crystal structures or drawing the claimed inference about the importance of those interactions. (LLM, conf=0.78)
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- Authors
- Walters, R. W., Agbandje-McKenna, M., Bowman, V. D., Moninger, T. O., Olson, N. H., Seiler, M., Chiorini, J. A., Baker, T. S., & Zabner, J.
- Affiliations
- University of Iowa (US)
- Department of Biochemistry and Molecular Biology, Center for Structural Biology, The Brain Institute, University of Florida College of Medicine, Gainesville, Florida 32610
- Purdue University West Lafayette (US)
- Departments of Internal Medicine
- National Institutes of Health (US)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2004-04
- Volume
- 78
- Issue
- 7
- Pages
- 3361-3371
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC371067
- OpenAlex
- W2037984334
- Cited by
- 114
- References
- 0
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 7 · 2014: 2 · 2013: 11 · 2012: 7
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (4r37gm033050-27)
- National Institute of General Medical Sciences (R01GM033050, R37GM-033050, GM-33050)
- National Institute of Allergy and Infectious Diseases (P01AI045976)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK54759, P30DK054759)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- sialic acid binding, AAV2, canine parvovirus, heparan sulfate proteoglycans, structure-function relationship
- MeSH terms
- Dependovirus, Amino Acid Sequence, Binding Sites, Capsid, Models, Molecular, Molecular Sequence Data, Parvovirus, N-Acetylneuraminic Acid, Cryoelectron Microscopy
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