Heparin binding induces conformational changes in Adeno-associated virus serotype 2
- 31 March 2009
- journal article
- Published by Elsevier BV in Journal of Structural Biology
- Vol. 165 (3), 146-156
- https://doi.org/10.1016/j.jsb.2008.12.002
Abstract
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 ∼18 Å 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.Keywords
This publication has 64 references indexed in Scilit:
- Safety and Efficacy of Gene Transfer for Leber's Congenital AmaurosisNew England Journal of Medicine, 2008
- Production, purification and preliminary X-ray crystallographic studies of adeno-associated virus serotype 7Acta Crystallographica Section F Structural Biology and Crystallization Communications, 2007
- Structure of Adeno-Associated Virus Serotype 8, a Gene Therapy VectorJournal of Virology, 2007
- Asymmetric binding of transferrin receptor to parvovirus capsidsProceedings of the National Academy of Sciences of the United States of America, 2007
- Structurally Mapping the Diverse Phenotype of Adeno-Associated Virus Serotype 4Journal of Virology, 2006
- Production, purification and preliminary X-ray crystallographic studies of adeno-associated virus serotype 1Acta Crystallographica Section F Structural Biology and Crystallization Communications, 2006
- Adeno-Associated Virus Type 2 Capsids with Externalized VP1/VP2 Trafficking Domains Are Generated prior to Passage through the Cytoplasm and Are Maintained until Uncoating Occurs in the NucleusJournal of Virology, 2006
- Adeno-Associated Virus Type 2 Contains an Integrin α5β1 Binding Domain Essential for Viral Cell EntryJournal of Virology, 2006
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994