| Structural highlights
Function
MU1_REOVL Major outer capsid protein involved in host cell membrane penetration. In the endocytic compartment, outer-capsid protein sigma-3 is removed by cathepsin proteases, which exposes the viral membrane-penetration protein mu-1. Both myristoylated peptides mu-1N and phi are released during infectious subvirion particles (ISVP) formation in the endosome. They associate with host membranes and mu-1N induces permeabilization and delivery of transcriptionally active viral particles into the host cell cytoplasm. Seems to induce apoptosis in the host cell.[1] [2] [3] [4] [5] The viral outer shell polypeptides, of which mu-1 is one, impose structural constraints that prevent elongation of nascent transcripts by the RNA-dependent RNA polymerase lambda-3.[6] [7] [8] [9] [10]
Publication Abstract from PubMed
Traditionally, molecular assembly pathways for viruses are inferred from high resolution structures of purified stable intermediates, low resolution images of cell sections and genetic approaches. Here, we directly visualise an unsuspected 'single shelled' intermediate for a mammalian orthoreovirus in cryo-preserved infected cells, by cryo-electron tomography of cellular lamellae. Particle classification and averaging yields structures to 5.6 A resolution, sufficient to identify secondary structural elements and produce an atomic model of the intermediate, comprising 120 copies each of protein lambda1 and sigma2. This lambda1 shell is 'collapsed' compared to the mature virions, with molecules pushed inwards at the icosahedral fivefolds by ~100 A, reminiscent of the first assembly intermediate of certain prokaryotic dsRNA viruses. This supports the supposition that these viruses share a common ancestor, and suggests mechanisms for the assembly of viruses of the Reoviridae. Such methodology holds promise for dissecting the replication cycle of many viruses.
Assembly intermediates of orthoreovirus captured in the cell.,Sutton G, Sun D, Fu X, Kotecha A, Hecksel CW, Clare DK, Zhang P, Stuart DI, Boyce M Nat Commun. 2020 Sep 7;11(1):4445. doi: 10.1038/s41467-020-18243-9. PMID:32895380[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Farsetta DL, Chandran K, Nibert ML. Transcriptional activities of reovirus RNA polymerase in recoated cores. Initiation and elongation are regulated by separate mechanisms. J Biol Chem. 2000 Dec 15;275(50):39693-701. PMID:11007773 doi:http://dx.doi.org/10.1074/jbc.M004562200
- ↑ Odegard AL, Chandran K, Zhang X, Parker JS, Baker TS, Nibert ML. Putative autocleavage of outer capsid protein micro1, allowing release of myristoylated peptide micro1N during particle uncoating, is critical for cell entry by reovirus. J Virol. 2004 Aug;78(16):8732-45. PMID:15280481 doi:http://dx.doi.org/10.1128/JVI.78.16.8732-8745.2004
- ↑ Coffey CM, Sheh A, Kim IS, Chandran K, Nibert ML, Parker JS. Reovirus outer capsid protein micro1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria. J Virol. 2006 Sep;80(17):8422-38. PMID:16912293 doi:http://dx.doi.org/80/17/8422
- ↑ Zhang L, Chandran K, Nibert ML, Harrison SC. Reovirus mu1 structural rearrangements that mediate membrane penetration. J Virol. 2006 Dec;80(24):12367-76. Epub 2006 Sep 27. PMID:17005655 doi:http://dx.doi.org/10.1128/JVI.01343-06
- ↑ Ivanovic T, Agosto MA, Zhang L, Chandran K, Harrison SC, Nibert ML. Peptides released from reovirus outer capsid form membrane pores that recruit virus particles. EMBO J. 2008 Apr 23;27(8):1289-98. Epub 2008 Mar 27. PMID:18369316 doi:http://dx.doi.org/emboj200860
- ↑ Farsetta DL, Chandran K, Nibert ML. Transcriptional activities of reovirus RNA polymerase in recoated cores. Initiation and elongation are regulated by separate mechanisms. J Biol Chem. 2000 Dec 15;275(50):39693-701. PMID:11007773 doi:http://dx.doi.org/10.1074/jbc.M004562200
- ↑ Odegard AL, Chandran K, Zhang X, Parker JS, Baker TS, Nibert ML. Putative autocleavage of outer capsid protein micro1, allowing release of myristoylated peptide micro1N during particle uncoating, is critical for cell entry by reovirus. J Virol. 2004 Aug;78(16):8732-45. PMID:15280481 doi:http://dx.doi.org/10.1128/JVI.78.16.8732-8745.2004
- ↑ Coffey CM, Sheh A, Kim IS, Chandran K, Nibert ML, Parker JS. Reovirus outer capsid protein micro1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria. J Virol. 2006 Sep;80(17):8422-38. PMID:16912293 doi:http://dx.doi.org/80/17/8422
- ↑ Zhang L, Chandran K, Nibert ML, Harrison SC. Reovirus mu1 structural rearrangements that mediate membrane penetration. J Virol. 2006 Dec;80(24):12367-76. Epub 2006 Sep 27. PMID:17005655 doi:http://dx.doi.org/10.1128/JVI.01343-06
- ↑ Ivanovic T, Agosto MA, Zhang L, Chandran K, Harrison SC, Nibert ML. Peptides released from reovirus outer capsid form membrane pores that recruit virus particles. EMBO J. 2008 Apr 23;27(8):1289-98. Epub 2008 Mar 27. PMID:18369316 doi:http://dx.doi.org/emboj200860
- ↑ Sutton G, Sun D, Fu X, Kotecha A, Hecksel CW, Clare DK, Zhang P, Stuart DI, Boyce M. Assembly intermediates of orthoreovirus captured in the cell. Nat Commun. 2020 Sep 7;11(1):4445. PMID:32895380 doi:10.1038/s41467-020-18243-9
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