title: VP5* rearranges when rotavirus uncoats.
abstract: Trypsin primes rotavirus for efficient infectivity by cleaving the spike protein, VP4, into VP8* and VP5*. A recombinant VP5* fragment has a trimeric, folded-back structure. Comparison of this structure with virion spikes suggests that a rearrangement, analogous to those of enveloped virus fusion proteins, may mediate membrane penetration by rotavirus during entry. To detect this inferred rearrangement of virion-associated authentic VP5*, we raised conformation-specific monoclonal antibodies against the recombinant VP5* fragment in its putative post-membrane penetration conformation. Using one of these antibodies, we demonstrate that rotavirus uncoating triggers a conformational change in the cleaved VP4 spike to yield rearranged VP5*.
authors.affiliation: Laboratory of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Yoder
authors.forename: Shane D
authors.initials: SD
authors.lastname: Trask
authors.forename: T Phuoc
authors.initials: TP
authors.lastname: Vo
authors.forename: Mawuena
authors.initials: M
authors.lastname: Binka
authors.forename: Ningguo
authors.initials: N
authors.lastname: Feng
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
authors.forename: Philip R
authors.initials: PR
authors.lastname: Dormitzer
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D012401:Rotavirus / Q000378:metabolism* / Q000648:ultrastructure; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure; D053586:Virus Internalization
chemical_list: D017361:Viral Nonstructural Proteins; C104282:nsp1 protein, Rotavirus
references.citation: J Virol. 2006 Nov;80(22):11293-304
references.pmid: 16971442
references.citation: Arch Virol. 1979;60(3-4):177-86
references.pmid: 41504
references.citation: J Virol. 1981 Sep;39(3):879-88
references.pmid: 6270356
references.citation: Electrophoresis. 1991 Jan;12(1):28-39
references.pmid: 2050096
references.citation: Biochemistry. 1981 Jan 6;20(1):33-7
references.pmid: 7470476
references.citation: Science. 2009 Jun 12;324(5933):1444-7
references.pmid: 19520960
references.citation: EMBO J. 2002 Mar 1;21(5):885-97
references.pmid: 11867517
references.citation: J Virol. 2009 Feb;83(4):1754-66
references.pmid: 19036817
references.citation: J Clin Microbiol. 1993 Mar;31(3):622-8
references.pmid: 7681440
references.citation: J Mol Biol. 2001 Apr 13;307(5):1171-9
references.pmid: 11292333
references.citation: Virology. 1992 Aug;189(2):828-32
references.pmid: 1322608
references.citation: EMBO J. 1996 Apr 1;15(7):1507-14
references.pmid: 8612573
references.citation: Virology. 1992 Mar;187(1):18-32
references.pmid: 1371025
references.citation: J Virol. 2002 Jan;76(2):552-9
references.pmid: 11752146
references.citation: J Virol. 2001 Aug;75(16):7339-50
references.pmid: 11462006
references.citation: J Virol. 2002 Jul;76(13):6643-51
references.pmid: 12050377
references.citation: Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12205-9
references.pmid: 8618870
references.citation: J Gen Virol. 1999 Apr;80 ( Pt 4):943-948
references.pmid: 10211964
references.citation: Virology. 1994 Oct;204(1):391-402
references.pmid: 7522373
references.citation: Nature. 2004 Aug 26;430(7003):1053-8
references.pmid: 15329727
references.citation: Virology. 2000 Nov 25;277(2):420-8
references.pmid: 11080489
references.citation: Virology. 1986 Dec;155(2):434-51
references.pmid: 2431540
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10644-8
references.pmid: 19487668
references.citation: J Virol. 2001 Jul;75(13):6052-61
references.pmid: 11390607
references.citation: EMBO J. 2006 Apr 5;25(7):1559-68
references.pmid: 16511559