The DOI matches its Crossref record; 72 of the 76 references it cites were found in a registry or an index.
Heparin binding induces conformational changes in Adeno-associated virus serotype 2
Open accessAbstract
Adeno-associated virus serotype 2 (AAV2) uses heparan sulfate proteoglycan as a cell surface-attachment receptor. In this study the structures of AAV2 alone and complexed with heparin were determined to approximately 18A resolution using cryo-electron microscopy and three-dimensional image reconstruction. A difference map showed positive density, modeled as heparin, close to the icosahedral twofold axes and between the protrusions that surround the threefold axes of the capsid. Regions of the model near the threefold place the receptor in close proximity to basic residues previously identified as part of the heparin binding site. The region of the model near the twofold axes identifies a second contact site, not previously characterized but which is also possibly configured by heparin binding. The difference map also revealed two significant conformational changes: (I) at the tops of the threefold protrusions, which have become flattened in the complex, and (II) at the fivefold axes where the top of the channel is widened possibly in response to movement of the HI loops in the capsid proteins. Ordered density in the interior of the capsid in the AAV2-heparin complex was interpreted as nucleic acid, consistent with the presence of non-viral DNA in the expressed capsids.
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“For example, for AAV2, two critical residues required for binding HS, R585 and R588, reside within VR-VIII, and the 511-NGR-513 proposed to play a role in α5β1 co-receptor binding is flanked by VR-I and VR-IV (Asokan et al., 2006; Kern et al., 2003; Levy et al., 2009; Ng et al., 2010; Opie et al., 2003; Shen et al., 2015; Summerford and Samulski, 1998).”
From Structure comparison of the chimeric AAV2.7m8 vector with parental AAV2 (2020) · cites this paper as Levy et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“different types of contaminating DNA sequences have been described as being copackaged with the transgenes, including fragments of the host cell genome from the cells that are used during vector production [81].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [81]
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Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
The CCP4 suite: programs for protein crystallography
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“The two resultant, essentially identical, difference density maps were inspected using Chimera (Pettersen et al., 2004) and O (Jones et al., 1991).”
MethodSafety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145 · cited 1×
“Extrusion and activity of the VP1-N terminal PLA2 domain is essential for efficient infection and is believed to occur during or shortly after virus entry into the cell (Bleker et al., 2005; Farr et al., 2006; Mani et al., 2006; Suikkanen et al., 2003; Vihinen-Ranta et al., 2002).”
BackgroundSummerford, C., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.2.1438-1445.1998 · Cited by 1,409 · cited 2×
“Heparan sulfate proteoglycan, the first receptor identified for an AAV virus (Summerford and Samulski, 1998), functions during infection to attach AAV2 and AAV3 to the cell surface.”
BackgroundKay, M. A., Manno, C. S., Ragni, M. V., Larson, P. J., Couto, L. B., McClelland, A., Glader, B. E., Chew, A. K., Tai, S. J., Herzog, R. W., et al. (2000) · Nature Genetics · doi:10.1038/73464 · Cited by 1,019 · cited 7×
“AAV2 residues R484, R487, K527, K532, R585, and R588 have been shown to affect heparin binding in mutagenesis studies (Kern et al., 2003; Opie et al., 2003; Wu et al., 2000).”
BackgroundInfluentialHeparin Structure and Interactions with Basic Fibroblast Growth Factor
Faham, S., Hileman, R. E., Fromm, J. R., Linhardt, R. J., & Rees, D. C. (1996) · Science · doi:10.1126/science.271.5252.1116 · Cited by 798 · cited 2×
“Heparin molecules, extracted from the atomic coordinates of the structure of a heparin hexasaccharide complexed with fibroblast growth factor (FGF- heparin) (Faham et al., 1996) (PDB Accession No.”
BackgroundαVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection
Summerford, C., Bartlett, J. S., & Samulski, R. J. (1999) · Nature Medicine · doi:10.1038/4768 · Cited by 711 · cited 2×
“Efficient AAV2 infection also requires a co-receptor, such as human fibroblast growth factor receptor 1 (FGFR1), integrins avb5 and a5b1, or hepatocyte growth factor receptor (Asokan et al., 2006; Kashiwakura et al., 2005; Summerford et al., 1999; Qing et al., 1999).”
BackgroundSpeir, J. A., Munshi, S. K., Wang, G., Baker, T. S., & Johnson, J. E. (1995) · Structure · doi:10.1016/s0969-2126(01)00135-6 · Cited by 698 · cited 1×
“Bink and Pleij, 2002; Prasad et al., 1994; Speir et al., 1995; Tang et al., 2001).”
Self-citationThe atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy
Xie, Q., Bu, W., Bhatia, S., Hare, J., Somasundaram, T., Azzi, A., & Chapman, M. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162250899 · Cited by 612
Cited by
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Virus-like particles in vaccine development
Roldão, A., Mellado, M. C. M., Castilho, L. R., Carrondo, M. J. T., & Alves, P. M. (2010) · Expert Review of Vaccines · doi:10.1586/erv.10.115 · Cited by 851
Pharmacology of Heparin and Related Drugs
Mulloy, B., Hogwood, J., Gray, E., Lever, R., & Page, C. P. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.011247 · Cited by 355
“The second study (Levy et al., 2009), using a partially depolymerized heparin, suffered the same problems, perhaps to a lesser extent; however, both studies agreed on the location of the major heparin binding site in the valleys between protrusions at the 3-fold axis of the icosahedral capsid.”
MethodResultAsokan, A., Conway, J. C., Phillips, J. L., Li, C., Hegge, J., Sinnott, R., Yadav, S. S., DiPrimio, N., Nam, H. J., Agbandje‐McKenna, M., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1599 · Cited by 270
Self-citationCapsid modifications for targeting and improving the efficacy of AAV vectors
Büning, H., & Srivastava, A. (2019) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.01.008 · Cited by 260
“Receptor binding not only enables cell entry, but also primes the capsid for the later release of its genetic payload (uncoating)(46) and prepares the cell for viral particle transport and processing.(46) Since AAV serotypes differ in receptors used for cell attachment and internalization, serotypes other than AAV2, t…”
Intracellular transport of recombinant adeno-associated virus vectors
Nonnenmacher, M., & Weber, T. (2012) · Gene Therapy · doi:10.1038/gt.2012.6 · Cited by 258
Metadata
- Authors
- Levy, H. C., Bowman, V. D., Govindasamy, L., McKenna, R., Nash, K., Warrington, K., Chen, W., Muzyczka, N., Yan, X., Baker, T. S., & Agbandje-McKenna, M.
- Affiliations
- University of Florida (US)
- Purdue University West Lafayette (US)
- University of California San Diego (US)
- Venue
- Journal of Structural Biology
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 165
- Issue
- 3
- Pages
- 146-156
- ISSN
- 1047-8477 (ISSN-L)
- PMC
- PMC3694330
- OpenAlex
- W2156683693
- Cited by
- 110
- References
- 76
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 3 · 2019: 10 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 11 · 2012: 10
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (4r37gm033050-27)
- National Heart, Lung, and Blood Institute (P01HL059412, P01HL051811)
- National Institute of General Medical Sciences (R37GM-033050)
- National Institute of Allergy and Infectious Diseases (P01AI045976)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Keywords
- AAV2, heparin binding, capsid conformational change, heparan sulfate proteoglycans, capsid structure
- MeSH terms
- Dependovirus, Capsid, Heparin, Image Processing, Computer-Assisted, Models, Molecular, Protein Conformation, Virion, Mutagenesis, Site-Directed, Nucleocapsid, Cryoelectron Microscopy, Capsid Proteins
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