PMID- 22496238
OWN - NLM
STAT- MEDLINE
DCOM- 20120809
LR  - 20240417
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 86
IP  - 12
DP  - 2012 Jun
TI  - Structural insight into the unique properties of adeno-associated virus serotype 
      9.
PG  - 6947-58
LID - 10.1128/JVI.07232-11 [doi]
AB  - Adeno-associated virus serotype 9 (AAV9) has enhanced capsid-associated tropism 
      for cardiac muscle and the ability to cross the blood-brain barrier compared to 
      other AAV serotypes. To help identify the structural features facilitating these 
      properties, we have used cryo-electron microscopy (cryo-EM) and three-dimensional 
      image reconstruction (cryo-reconstruction) and X-ray crystallography to determine 
      the structure of the AAV9 capsid at 9.7- and 2.8-A resolutions, respectively. The 
      AAV9 capsid exhibits the surface topology conserved in all AAVs: depressions at 
      each icosahedral two-fold symmetry axis and surrounding each five-fold axis, 
      three separate protrusions surrounding each three-fold axis, and a channel at 
      each five-fold axis. The AAV9 viral protein (VP) has a conserved core structure, 
      consisting of an eight-stranded, beta-barrel motif and the alphaA helix, which are 
      present in all parvovirus structures. The AAV9 VP differs in nine variable 
      surface regions (VR-I to -IX) compared to AAV4, but at only three (VR-I, VR-II, 
      and VR-IV) compared to AAV2 and AAV8. VR-I differences modify the raised region 
      of the capsid surface between the two-fold and five-fold depressions. The VR-IV 
      difference produces smaller three-fold protrusions in AAV9 that are less 
      "pointed" than AAV2 and AAV8. Significantly, residues in the AAV9 VRs have been 
      identified as important determinants of cellular tropism and transduction and 
      dictate its antigenic diversity from AAV2. Hence, the AAV9 VRs likely confer the 
      unique infection phenotypes of this serotype.
FAU - DiMattia, Michael A
AU  - DiMattia MA
AD  - Department of Biochemistry and Molecular Biology, Center for Structural Biology, 
      McKnight Brain Institute, College of Medicine, University of Florida, 
      Gainesville, Florida, USA.
FAU - Nam, Hyun-Joo
AU  - Nam HJ
FAU - Van Vliet, Kim
AU  - Van Vliet K
FAU - Mitchell, Matthew
AU  - Mitchell M
FAU - Bennett, Antonette
AU  - Bennett A
FAU - Gurda, Brittney L
AU  - Gurda BL
FAU - McKenna, Robert
AU  - McKenna R
FAU - Olson, Norman H
AU  - Olson NH
FAU - Sinkovits, Robert S
AU  - Sinkovits RS
FAU - Potter, Mark
AU  - Potter M
FAU - Byrne, Barry J
AU  - Byrne BJ
FAU - Aslanidi, George
AU  - Aslanidi G
FAU - Zolotukhin, Sergei
AU  - Zolotukhin S
FAU - Muzyczka, Nicholas
AU  - Muzyczka N
FAU - Baker, Timothy S
AU  - Baker TS
FAU - Agbandje-McKenna, Mavis
AU  - Agbandje-McKenna M
LA  - eng
SI  - PDB/3UX1
GR  - R37 GM033050/GM/NIGMS NIH HHS/United States
GR  - R01 GM082946/GM/NIGMS NIH HHS/United States
GR  - P01 HL59412/HL/NHLBI NIH HHS/United States
GR  - P41 RR001646/RR/NCRR NIH HHS/United States
GR  - DMR0225180/GM/NIGMS NIH HHS/United States
GR  - P41 RR001081/RR/NCRR NIH HHS/United States
GR  - S10 RR020016/RR/NCRR NIH HHS/United States
GR  - R37 GM-33050/GM/NIGMS NIH HHS/United States
GR  - 1S10 RR020016/RR/NCRR NIH HHS/United States
GR  - P01 HL059412/HL/NHLBI NIH HHS/United States
GR  - RR-01646/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20120411
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Capsid Proteins)
SB  - IM
MH  - Capsid/*chemistry/metabolism
MH  - Capsid Proteins/chemistry/genetics/metabolism
MH  - Cryoelectron Microscopy
MH  - Crystallography, X-Ray
MH  - Dependovirus/*chemistry/classification/genetics/metabolism
MH  - Imaging, Three-Dimensional
PMC - PMC3393551
EDAT- 2012/04/13 06:00
MHDA- 2012/08/10 06:00
PMCR- 2012/12/01
CRDT- 2012/04/13 06:00
PHST- 2012/04/13 06:00 [entrez]
PHST- 2012/04/13 06:00 [pubmed]
PHST- 2012/08/10 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - JVI.07232-11 [pii]
AID - 07232-11 [pii]
AID - 10.1128/JVI.07232-11 [doi]
PST - ppublish
SO  - J Virol. 2012 Jun;86(12):6947-58. doi: 10.1128/JVI.07232-11. Epub 2012 Apr 11.