2g8g
From Proteopedia
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'''Structurally mapping the diverse phenotype of Adeno-Associated Virus serotype 4''' | '''Structurally mapping the diverse phenotype of Adeno-Associated Virus serotype 4''' | ||
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[[Category: Muzyczka, N.]] | [[Category: Muzyczka, N.]] | ||
[[Category: Padron, E.]] | [[Category: Padron, E.]] | ||
| - | [[Category: | + | [[Category: Adeno-associated virus serotype 4]] |
| - | [[Category: | + | [[Category: Gene therapy]] |
| - | [[Category: | + | [[Category: Icosahedral virus]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:49:06 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 01:49, 4 May 2008
Structurally mapping the diverse phenotype of Adeno-Associated Virus serotype 4
Overview
The adeno-associated viruses (AAVs) can package and deliver foreign DNA into cells for corrective gene delivery applications. The AAV serotypes have distinct cell binding, transduction, and antigenic characteristics that have been shown to be dictated by the capsid viral protein (VP) sequence. To understand the contribution of capsid structure to these properties, we have determined the crystal structure of AAV serotype 4 (AAV4), one of the most diverse serotypes with respect to capsid protein sequence and antigenic reactivity. Structural comparison of AAV4 to AAV2 shows conservation of the core beta strands (betaB to betaI) and helical (alphaA) secondary structure elements, which also exist in all other known parvovirus structures. However, surface loop variations (I to IX), some containing compensating structural insertions and deletions in adjacent regions, result in local topological differences on the capsid surface. These include AAV4 having a deeper twofold depression, wider and rounder protrusions surrounding the threefold axes, and a different topology at the top of the fivefold channel from that of AAV2. Also, the previously observed "valleys" between the threefold protrusions, containing AAV2's heparin binding residues, are narrower in AAV4. The observed differences in loop topologies at subunit interfaces are consistent with the inability of AAV2 and AAV4 VPs to combine for mosaic capsid formation in efforts to engineer novel tropisms. Significantly, all of the surface loop variations are associated with amino acids reported to affect receptor recognition, transduction, and anticapsid antibody reactivity for AAV2. This observation suggests that these capsid regions may also play similar roles in the other AAV serotypes.
About this Structure
2G8G is a Single protein structure of sequence from Viruses. Full crystallographic information is available from OCA.
Reference
Structurally mapping the diverse phenotype of adeno-associated virus serotype 4., Govindasamy L, Padron E, McKenna R, Muzyczka N, Kaludov N, Chiorini JA, Agbandje-McKenna M, J Virol. 2006 Dec;80(23):11556-70. Epub 2006 Sep 13. PMID:16971437 Page seeded by OCA on Sun May 4 04:49:06 2008
