Heparin binding induces conformational changes in Adeno-associated virus serotype 2

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 ∼18Å resolution using cryo-electron microscopy and three-dimensional image reconstruction. A diff...

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Bibliographic Details
Published in:Journal of structural biology 2009-03, Vol.165 (3), p.146-156
Main Authors: Levy, Hazel C., Bowman, Valorie D., Govindasamy, Lakshmanan, McKenna, Robert, Nash, Kevin, Warrington, Kenneth, Chen, Weijun, Muzyczka, Nicholas, Yan, Xiaodong, Baker, Timothy S., Agbandje-McKenna, Mavis
Format: Article
Language:English
Subjects:
3D image reconstruction
Adeno-associated virus
Atomic modeling
Capsid - chemistry
Capsid Proteins - chemistry
Cryoelectron Microscopy
Dependovirus - chemistry
Electron cryo-microscopy
Heparin - chemistry
Heparin sulfate
Image Processing, Computer-Assisted
Models, Molecular
Mutagenesis, Site-Directed
Nucleocapsid - chemistry
Parvovirus
Protein Conformation
Receptor attachment
Virion - chemistry
Virus structure
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Summary: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 ∼18Å 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.
ISSN:1047-8477
1095-8657
DOI:10.1016/j.jsb.2008.12.002