Reovirus μ1 structural rearrangements that mediate membrane penetration

Lan Zhang, Kartik Chandran, Max L. Nibert, Stephen C. Harrison

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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 σ3 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 α-helix content. We have identified a protease-resistant ∼23-kDa fragment of μ1*, which contains the largely α-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 β-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.

Original languageEnglish (US)
Pages (from-to)12367-12376
Number of pages10
JournalJournal of virology
Volume80
Issue number24
DOIs
StatePublished - Dec 2006
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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