PMID- 21463638
OWN - NLM
STAT- MEDLINE
DCOM- 20110803
LR  - 20110520
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 409
IP  - 3
DP  - 2011 Jun 10
TI  - Conformational changes in adeno-associated virus type 1 induced by genome 
      packaging.
PG  - 427-38
LID - 10.1016/j.jmb.2011.03.062 [doi]
AB  - Adeno-associated virus (AAV) is frequently used as a vector for gene therapy. The 
      viral capsid consists of three structural proteins (VP1, VP2, and VP3) that have 
      a common C-terminal core (VP3), with N-terminal extensions of increasing length 
      in VP2 and VP1. The capsid encloses a single-stranded genome of up to 4.7 kb, 
      which is packaged into empty capsids. The N-terminal extension of VP1 carries a 
      phospholipase domain that becomes accessible during infection in the endosomal 
      pathway. We have used cryo-electron microscopy and image reconstruction to 
      determine subnanometer-resolution structures of recombinant AAV1 that has 
      packaged different amounts of a 3.6-kb recombinant genome. The maps show that the 
      AAV1 capsid undergoes continuous conformational changes upon packaging of the 
      genome. The rearrangements occur at the inner capsid surface and lead to 
      constrictions of the pores at the 5-fold symmetry axes and to subtle movements of 
      the beta-sheet regions of the capsid proteins. In fully packaged particles, the 
      genome forms stem-like features that contact the inner capsid surface at the 
      3-fold symmetry axes. We think that the reorganization of the inner surface has 
      an impact on the viral life cycle during infection, preparing the externalization 
      of phospholipase domains through the pores at the 5-fold symmetry axes and 
      possibly genome release.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Gerlach, Britta
AU  - Gerlach B
AD  - Division of Tumor Virology, German Cancer Research Center, Im Neuenheimerfeld, 
      Heidelberg, Germany.
FAU - Kleinschmidt, Jurgen A
AU  - Kleinschmidt JA
FAU - Bottcher, Bettina
AU  - Bottcher B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110402
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Capsid Proteins)
SB  - IM
MH  - Capsid/ultrastructure
MH  - Capsid Proteins/ultrastructure
MH  - Cryoelectron Microscopy/methods
MH  - Dependovirus/*chemistry/*genetics/ultrastructure
MH  - *Genome, Viral
MH  - Image Processing, Computer-Assisted/methods
MH  - Models, Molecular
MH  - Protein Conformation
MH  - *Virus Assembly
EDAT- 2011/04/06 06:00
MHDA- 2011/08/04 06:00
CRDT- 2011/04/06 06:00
PHST- 2010/11/29 00:00 [received]
PHST- 2011/03/21 00:00 [revised]
PHST- 2011/03/28 00:00 [accepted]
PHST- 2011/04/06 06:00 [entrez]
PHST- 2011/04/06 06:00 [pubmed]
PHST- 2011/08/04 06:00 [medline]
AID - S0022-2836(11)00351-2 [pii]
AID - 10.1016/j.jmb.2011.03.062 [doi]
PST - ppublish
SO  - J Mol Biol. 2011 Jun 10;409(3):427-38. doi: 10.1016/j.jmb.2011.03.062. Epub 2011 
      Apr 2.