Journal of Virology, May 2005, p. 5296-5303, Vol. 79, No. 9
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.9.5296-5303.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
A Conformational Change in the Adeno-Associated Virus Type 2 Capsid Leads to the Exposure of Hidden VP1 N Termini
Stephanie Kronenberg,1,2,
Bettina Böttcher,
Claus W. von der Lieth,3
Svenja Bleker,1 and
Jürgen A. Kleinschmidt1*
German Cancer Research Centre, Tumor Virology,1
Central Spectroscopy,2
European Molecular Biology Laboratory Heidelberg, Structural and Computational Biology Programme, Heidelberg, Germany3
Received 20 September 2004/
Accepted 16 December 2004
The complex infection process of parvoviruses is not well understood so far. An important role has been attributed to a phospholipase A2 domain which is located within the unique N terminus of the capsid protein VP1. Based on the structural difference between adeno-associated virus type 2 wild-type capsids and capsids lacking VP1 or VP2, we show via electron cryomicroscopy that the N termini of VP1 and VP2 are involved in forming globules inside the capsids of empty and full particles. Upon limited heat shock, VP1 and possibly VP2 become exposed on the outsides of full but not empty capsids, which is correlated with the disappearance of the globules in the inner surfaces of the capsids. Using molecular modeling, we discuss the constraints on the release of the globularly organized VP1-unique N termini through the channels at the fivefold symmetry axes outside of the capsid.
* Corresponding author. Mailing address: Applied Tumor Virology, German Cancer Research Centre, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. Phone: 49 6221 424978. Fax: 49 6221 424962. E-mail: J.Kleinschmidt{at}DKFZ-Heidelberg.de.
S.K. and B.B. contributed equally to this work.
Journal of Virology, May 2005, p. 5296-5303, Vol. 79, No. 9
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.9.5296-5303.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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Copyright © 2005 by the American Society for Microbiology. All rights reserved.