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TitleCryo-EM structure of adeno-associated virus 4 at 2.2 Å resolution.
Journal, issue, pagesActa Crystallogr D Struct Biol, Vol. 79, Issue Pt 2, Page 140-153, Year 2023
Publish dateFeb 1, 2023
AuthorsGrant Zane / Mark Silveria / Nancy Meyer / Tommi White / Rui Duan / Xiaoqin Zou / Michael Chapman /
PubMed AbstractAdeno-associated virus (AAV) is the vector of choice for several approved gene-therapy treatments and is the basis for many ongoing clinical trials. Various strains of AAV exist (referred to as ...Adeno-associated virus (AAV) is the vector of choice for several approved gene-therapy treatments and is the basis for many ongoing clinical trials. Various strains of AAV exist (referred to as serotypes), each with their own transfection characteristics. Here, a high-resolution cryo-electron microscopy structure (2.2 Å) of AAV serotype 4 (AAV4) is presented. The receptor responsible for transduction of the AAV4 clade of AAV viruses (including AAV11, AAV12 and AAVrh32.33) is unknown. Other AAVs interact with the same cell receptor, adeno-associated virus receptor (AAVR), in one of two different ways. AAV5-like viruses interact exclusively with the polycystic kidney disease-like 1 (PKD1) domain of AAVR, while most other AAVs interact primarily with the PKD2 domain. A comparison of the present AAV4 structure with prior corresponding structures of AAV5, AAV2 and AAV1 in complex with AAVR provides a foundation for understanding why the AAV4-like clade is unable to interact with either PKD1 or PKD2 of AAVR. The conformation of the AAV4 capsid in variable regions I, III, IV and V on the viral surface appears to be sufficiently different from AAV2 to ablate binding with PKD2. Differences between AAV4 and AAV5 in variable region VII appear to be sufficient to exclude binding with PKD1.
External linksActa Crystallogr D Struct Biol / PubMed:36762860 / PubMed Central
MethodsEM (single particle)
Resolution2.21 Å
Structure data

EMDB-25903, PDB-7thr:
Cryo-electron microscopy of Adeno-associated virus serotype 4 at 2.2 A
Method: EM (single particle) / Resolution: 2.21 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

Source
  • adeno-associated virus - 4
KeywordsVIRUS LIKE PARTICLE / AAV4 / adeno-associated virus / serotype 4

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