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Journal of Virology, December 2006, p. 12367-12376, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01343-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Reovirus µ1 Structural Rearrangements That Mediate Membrane Penetration{triangledown}

Lan Zhang,1 Kartik Chandran,2,{dagger} Max L. Nibert,2 and Stephen C. Harrison1,3*

Department of Molecular Medicine,1 Howard Hughes Medical Institute, Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115,3 Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 021152

Received 26 June 2006/ Accepted 20 September 2006

Membrane penetration by nonenveloped reoviruses is mediated by the outer-capsid protein, µ1 (76 kDa). Previous evidence has suggested that an autolytic cleavage in µ1 allows the release of its N-terminally myristoylated peptide, µ1N (4 kDa), which probably then interacts with the target-cell membrane. A substantial rearrangement of the remaining portion of µ1, µ1C (72 kDa), must also have occurred for µ1N to be released, and some regions in µ1C may make additional contacts with the membrane. We describe here a particle-free system to study conformational rearrangements of µ1. We show that removal of the protector protein {sigma}3 is not sufficient to trigger rearrangement of free µ1 trimer and that free µ1 trimer undergoes conformational changes similar to those of particle-associated µ1 when induced by similar conditions. The µ1 rearrangements require separation of the µ1 trimer head domains but not the µ1N/C autocleavage. We have also obtained a relatively homogeneous form of the structurally rearranged µ1 (µ1*) in solution. It is an elongated monomer and retains substantial {alpha}-helix content. We have identified a protease-resistant ~23-kDa fragment of µ1*, which contains the largely {alpha}-helical regions designated domains I and II in the conformation of µ1 prior to rearrangement. We propose that the µ1 conformational changes preceding membrane penetration or disruption during cell entry involve (i) separation of the ß-barrel head domains in the µ1 trimer, (ii) autolytic cleavage at the µ1N/C junction, associated with partial unfolding of µ1C and release of µ1N, and (iii) refolding of the N-terminal helical domains of µ1C, with which µ1N was previously complexed, accompanied by dissociation of the µ1 trimer.

* Corresponding author. Mailing address: Children's Hospital, Enders 673, 320 Longwood Avenue, Boston, MA 02115. Phone: (617) 355-7372. Fax: (617) 730-1967. E-mail: Harrison{at}crystal.harvard.edu.

{triangledown} Published ahead of print on 27 September 2006.

{dagger} Present address: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Karp Family Research Laboratories, 1 Blackfan Circle, Boston, MA 02115.

Journal of Virology, December 2006, p. 12367-12376, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01343-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhang, L., Agosto, M. A., Ivanovic, T., King, D. S., Nibert, M. L., Harrison, S. C. (2009). Requirements for the Formation of Membrane Pores by the Reovirus Myristoylated {micro}1N Peptide. J. Virol. 83: 7004-7014 [Abstract] [Full Text]  
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  • Galloux, M., Libersou/, S., Morellet, N., Bouaziz, S., Da Costa, B., Ouldali, M., Lepault, J., Delmas, B. (2007). Infectious Bursal Disease Virus, a Non-enveloped Virus, Possesses a Capsid-associated Peptide That Deforms and Perforates Biological Membranes. J. Biol. Chem. 282: 20774-20784 [Abstract] [Full Text]  


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