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Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features

The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image recons...

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Autores principales: Mietzsch, Mario, Jose, Ariana, Chipman, Paul, Bhattacharya, Nilakshee, Daneshparvar, Nadia, McKenna, Robert, Agbandje-McKenna, Mavis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828300/
https://www.ncbi.nlm.nih.gov/pubmed/33450892
http://dx.doi.org/10.3390/v13010101
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author Mietzsch, Mario
Jose, Ariana
Chipman, Paul
Bhattacharya, Nilakshee
Daneshparvar, Nadia
McKenna, Robert
Agbandje-McKenna, Mavis
author_facet Mietzsch, Mario
Jose, Ariana
Chipman, Paul
Bhattacharya, Nilakshee
Daneshparvar, Nadia
McKenna, Robert
Agbandje-McKenna, Mavis
author_sort Mietzsch, Mario
collection PubMed
description The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, 2.54, and 2.76 Å resolution, respectively. These structures complete the structural atlas of the AAV serotype capsids. AAV7 represents the first clade D capsid structure; AAV11 and AAV12 are of a currently unassigned clade that would include AAV4; and AAV13 represents the first AAV2-AAV3 hybrid clade C capsid structure. These newly determined capsid structures all exhibit the AAV capsid features including 5-fold channels, 3-fold protrusions, 2-fold depressions, and a nucleotide binding pocket with an ordered nucleotide in genome-containing capsids. However, these structures have viral proteins that display clade-specific loop conformations. This structural characterization completes our three-dimensional library of the current AAV serotypes to provide an atlas of surface loop configurations compatible with capsid assembly and amenable for future vector engineering efforts. Derived vectors could improve gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting.
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spelling pubmed-78283002021-01-25 Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features Mietzsch, Mario Jose, Ariana Chipman, Paul Bhattacharya, Nilakshee Daneshparvar, Nadia McKenna, Robert Agbandje-McKenna, Mavis Viruses Article The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, 2.54, and 2.76 Å resolution, respectively. These structures complete the structural atlas of the AAV serotype capsids. AAV7 represents the first clade D capsid structure; AAV11 and AAV12 are of a currently unassigned clade that would include AAV4; and AAV13 represents the first AAV2-AAV3 hybrid clade C capsid structure. These newly determined capsid structures all exhibit the AAV capsid features including 5-fold channels, 3-fold protrusions, 2-fold depressions, and a nucleotide binding pocket with an ordered nucleotide in genome-containing capsids. However, these structures have viral proteins that display clade-specific loop conformations. This structural characterization completes our three-dimensional library of the current AAV serotypes to provide an atlas of surface loop configurations compatible with capsid assembly and amenable for future vector engineering efforts. Derived vectors could improve gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting. MDPI 2021-01-13 /pmc/articles/PMC7828300/ /pubmed/33450892 http://dx.doi.org/10.3390/v13010101 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mietzsch, Mario
Jose, Ariana
Chipman, Paul
Bhattacharya, Nilakshee
Daneshparvar, Nadia
McKenna, Robert
Agbandje-McKenna, Mavis
Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features
title Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features
title_full Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features
title_fullStr Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features
title_full_unstemmed Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features
title_short Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features
title_sort completion of the aav structural atlas: serotype capsid structures reveals clade-specific features
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828300/
https://www.ncbi.nlm.nih.gov/pubmed/33450892
http://dx.doi.org/10.3390/v13010101
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