Structure of adeno-associated virus type 4.
Adeno-associated virus (AAV) is a member of the Parvoviridae, belonging to the Dependovirus genus. Currently, several distinct isolates of AAV are in development for use in human gene therapy applications due to their ability to transduce different target cells. The need to manipulate AAV capsids for specific tissue delivery has generated interest in understanding their capsid structures. The structure of AAV type 4 (AAV4), one of the most antigenically distinct serotypes, was determined to 13-A resolution by cryo-electron microscopy and image reconstruction. A pseudoatomic model was built for the AAV4 capsid by use of a structure-based sequence alignment of its major capsid protein, VP3, with that of AAV2, to which AAV4 is 58% identical and constrained by its reconstructed density envelope. The model showed variations in the surface loops that may account for the differences in receptor binding and antigenicity between AAV2 and AAV4. The AAV4 capsid surface topology also shows an unpredicted structural similarity to that of Aleutian mink disease virus and human parvovirus B19, autonomous members of the genus, despite limited sequence homology.
Padron
Eric
E
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Bowman
Valorie
V
Kaludov
Nikola
N
Govindasamy
Lakshmanan
L
Levy
Hazel
H
Nick
Phillip
P
McKenna
Robert
R
Muzyczka
Nicholas
N
Chiorini
John A
JA
Baker
Timothy S
TS
Agbandje-McKenna
Mavis
M
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002213:Capsid / Q000737:chemistry / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D020285:Cryoelectron Microscopy; D000229:Dependovirus / Q000648:ultrastructure*; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010321:Parvoviridae / Q000145:classification / Q000648:ultrastructure; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity