Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)
- Oregon HSU
Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- OSTI ID:
- 1033435
- Journal Information:
- Virology, Vol. 423, Issue (1) ; 02, 2012; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Adeno-associated virus-2 and its primary cellular receptor-Cryo-EM structure of a heparin complex
Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20