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Title: Structural Insights into Adeno-Associated Virus Serotype 5

Abstract

The adeno-associated viruses (AAVs) display differential cell binding, transduction, and antigenic characteristics specified by their capsid viral protein (VP) composition. Toward structure-function annotation, the crystal structure of AAV5, one of the most sequence diverse AAV serotypes, was determined to 3.45-Å resolution. The AAV5 VP and capsid conserve topological features previously described for other AAVs but uniquely differ in the surface-exposed HI loop between βH and βI of the core β-barrel motif and have pronounced conformational differences in two of the AAV surface variable regions (VRs), VR-IV and VR-VII. The HI loop is structurally conserved in other AAVs despite amino acid differences but is smaller in AAV5 due to an amino acid deletion. This HI loop is adjacent to VR-VII, which is largest in AAV5. The VR-IV, which forms the larger outermost finger-like loop contributing to the protrusions surrounding the icosahedral 3-fold axes of the AAVs, is shorter in AAV5, creating a smoother capsid surface topology. The HI loop plays a role in AAV capsid assembly and genome packaging, and VR-IV and VR-VII are associated with transduction and antigenic differences, respectively, between the AAVs. A comparison of interior capsid surface charge and volume of AAV5 to AAV2 and AAV4 showed amore » higher propensity of acidic residues but similar volumes, consistent with comparable DNA packaging capacities. Here, this structure provided a three-dimensional (3D) template for functional annotation of the AAV5 capsid with respect to regions that confer assembly efficiency, dictate cellular transduction phenotypes, and control antigenicity.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [1];  [1];  [1]
  1. Univ. of Florida, Gainesville, FL (United States)
  2. National Inst. of Health (NIH), Bethesda, MD (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF); National Inst. of Health; National Inst. of General Medical Sciences
OSTI Identifier:
1258696
Grant/Contract Number:  
AC02-98CH10886; W-31-109-Eng-38; DMR-0936384; GM-103485; R01 GM082946; P01 HL51811
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Virology
Additional Journal Information:
Journal Volume: 87; Journal Issue: 20; Journal ID: ISSN 0022-538X
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Govindasamy, Lakshmanan, DiMattia, Michael A., Gurda, Brittney L., Halder, Sujata, McKenna, Robert, Chiorini, John A., Muzyczka, Nicholas, Zolotukhin, Sergei, and Agbandje-McKenna, Mavis. Structural Insights into Adeno-Associated Virus Serotype 5. United States: N. p., 2013. Web. doi:10.1128/JVI.00867-13.
Govindasamy, Lakshmanan, DiMattia, Michael A., Gurda, Brittney L., Halder, Sujata, McKenna, Robert, Chiorini, John A., Muzyczka, Nicholas, Zolotukhin, Sergei, & Agbandje-McKenna, Mavis. Structural Insights into Adeno-Associated Virus Serotype 5. United States. https://doi.org/10.1128/JVI.00867-13
Govindasamy, Lakshmanan, DiMattia, Michael A., Gurda, Brittney L., Halder, Sujata, McKenna, Robert, Chiorini, John A., Muzyczka, Nicholas, Zolotukhin, Sergei, and Agbandje-McKenna, Mavis. 2013. "Structural Insights into Adeno-Associated Virus Serotype 5". United States. https://doi.org/10.1128/JVI.00867-13. https://www.osti.gov/servlets/purl/1258696.
@article{osti_1258696,
title = {Structural Insights into Adeno-Associated Virus Serotype 5},
author = {Govindasamy, Lakshmanan and DiMattia, Michael A. and Gurda, Brittney L. and Halder, Sujata and McKenna, Robert and Chiorini, John A. and Muzyczka, Nicholas and Zolotukhin, Sergei and Agbandje-McKenna, Mavis},
abstractNote = {The adeno-associated viruses (AAVs) display differential cell binding, transduction, and antigenic characteristics specified by their capsid viral protein (VP) composition. Toward structure-function annotation, the crystal structure of AAV5, one of the most sequence diverse AAV serotypes, was determined to 3.45-Å resolution. The AAV5 VP and capsid conserve topological features previously described for other AAVs but uniquely differ in the surface-exposed HI loop between βH and βI of the core β-barrel motif and have pronounced conformational differences in two of the AAV surface variable regions (VRs), VR-IV and VR-VII. The HI loop is structurally conserved in other AAVs despite amino acid differences but is smaller in AAV5 due to an amino acid deletion. This HI loop is adjacent to VR-VII, which is largest in AAV5. The VR-IV, which forms the larger outermost finger-like loop contributing to the protrusions surrounding the icosahedral 3-fold axes of the AAVs, is shorter in AAV5, creating a smoother capsid surface topology. The HI loop plays a role in AAV capsid assembly and genome packaging, and VR-IV and VR-VII are associated with transduction and antigenic differences, respectively, between the AAVs. A comparison of interior capsid surface charge and volume of AAV5 to AAV2 and AAV4 showed a higher propensity of acidic residues but similar volumes, consistent with comparable DNA packaging capacities. Here, this structure provided a three-dimensional (3D) template for functional annotation of the AAV5 capsid with respect to regions that confer assembly efficiency, dictate cellular transduction phenotypes, and control antigenicity.},
doi = {10.1128/JVI.00867-13},
url = {https://www.osti.gov/biblio/1258696}, journal = {Journal of Virology},
issn = {0022-538X},
number = 20,
volume = 87,
place = {United States},
year = {Fri Sep 20 00:00:00 EDT 2013},
month = {Fri Sep 20 00:00:00 EDT 2013}
}

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