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TitleCompletion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features.
Journal, issue, pagesViruses, Vol. 13, Issue 1, Year 2021
Publish dateJan 13, 2021
AuthorsMario Mietzsch / Ariana Jose / Paul Chipman / Nilakshee Bhattacharya / Nadia Daneshparvar / Robert McKenna / Mavis Agbandje-McKenna /
PubMed AbstractThe 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 ...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.
External linksViruses / PubMed:33450892 / PubMed Central
MethodsEM (single particle)
Resolution2.54 - 3.16 Å
Structure data

23189

7l5q

EMDB-23189, PDB-7l5q:
The empty AAV7 capsid
Method: EM (single particle) / Resolution: 2.96 Å

23190

7l5u

EMDB-23190, PDB-7l5u:
The full AAV7 capsid
Method: EM (single particle) / Resolution: 3.16 Å

23200

7l6a

EMDB-23200, PDB-7l6a:
The genome-containing AAV12 capsid
Method: EM (single particle) / Resolution: 2.67 Å

23201

7l6b

EMDB-23201, PDB-7l6b:
The empty AAV12 capsid
Method: EM (single particle) / Resolution: 2.54 Å

23202

7l6e

EMDB-23202, PDB-7l6e:
The genome-containing AAV11 capsid
Method: EM (single particle) / Resolution: 3.15 Å

23203

7l6f

EMDB-23203, PDB-7l6f:
The empty AAV11 capsid
Method: EM (single particle) / Resolution: 2.86 Å

23204

7l6h

EMDB-23204, PDB-7l6h:
The genome-containing AAV13 capsid
Method: EM (single particle) / Resolution: 3.0 Å

23205

7l6i

EMDB-23205, PDB-7l6i:
The empty AAV13 capsid
Method: EM (single particle) / Resolution: 2.76 Å

Chemicals

ChemComp-D5M:
2'-DEOXYADENOSINE-5'-MONOPHOSPHATE

Source
  • adeno-associated virus - 7
  • adeno-associated virus 12
  • adeno-associated virus 11
  • adeno-associated virus 13
KeywordsVIRUS / Icosahedral Capsid / AAV7 / Adeno-associated virus / Parvovirus / Gene Therapy / AAV12 / AAV11 / AAV13

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