Allosteric Signaling and a Nuclear Exit Strategy: Binding of UL25/UL17 Heterodimers to DNA-Filled HSV-1 Capsids

Trus, Benes L.; Newcomb, William W.; Cheng, Naiqian; Cardone, Giovanni; Marekov, Lyuben N.; Homa, Fred L.; Brown, Jay C.; Steven, Alasdair C.

doi:10.1016/j.molcel.2007.04.010

Cited by 155 publications

(232 citation statements)

References 47 publications

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“…The upper domains of triplex proteins in alpha-herpesvirus and beta-herpesvirus also bind different tegument densities, a defining feature of specific capsid-tegument associations The upper domain of TRI-1 is highly divergent across different herpesvirus subfamilies; for instance, the structure of the HSV-1 TRI-1 homolog, VP19c, is substantially larger, consistent with across different herpesvirus subfamilies Zhou et al, 1999;Liu and Zhou, 2007;Trus et al, 2007;Conway et al, 2010;Toropova et al, 2011;Homa et al, 2013).…”

Section: Discussionmentioning

confidence: 83%

“…In CMV, the inner tegument layer consists of highly organized fi lamentous proteins interacting with the pentons, hexons and triplexes of the capsid Trus et al, 1999;Mettenleiter, 2002). Whereas in alpha-herpesviruses, tegument proteins bind only to pentons and its 10 surrounding triplexes Liu and Zhou, 2007;Trus et al, 2007;Conway et al, 2010;Toropova et al, 2011;Homa et al, 2013). Thus, the observed structural difference in the MCP upper domain (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM

et al. 2013

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Cytomegalovirus (CMV) is distinct among members of the Herpesviridae family for having the largest dsDNA genome (230 kb). Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid, but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described. Here, we report a cryo electron microscopy (cryoEM) structure of the murine cytomegalovirus (MCMV) capsid at a 9.1 Å resolution and describe the molecular interactions among the ~3000 protein molecules in the MCMV capsid at the secondary structure level. Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling. The major capsid protein (MCP) upper domain (MCPud) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identifi ed as a "saddle loop" region, located at the tip of MCPud and involved in interaction with the smallest capsid protein (SCP). Interactions among the bacteriophage HK97-like fl oor domain of MCP, the middle domain of MCP, the hook and clamp domains of the triplex proteins (hoop and clamp domains of TRI-1 and clamp domain of TRI-2) contribute to the formation of a mature capsid. These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attaching unique functional tegument proteins outside.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM

et al. 2013

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“…reportedly interacts with the triplex protein VP19c, as well as the major capsid protein VP5 (240,316). Accumulation of UL25 protein may reinforce the capsid to prevent loss of DNA, similar to the role of accessory proteins in dsDNA bacteriophages (203,231).…”

Section: Herpesvirus Replicationmentioning

confidence: 95%

“…The capsid-associated protein encoded by UL25 (ORF19) is present on A, B, C capsids as well as virions (231,285). UL25 forms a heterodimer with UL17 and attaches to the exterior capsid vertices (310,316). Additionally, UL25…”

Section: Herpesvirus Replicationmentioning

confidence: 99%

“…In HSV-1 the proteins encoded by UL17 and UL25 manage DNA packaging and retention (58,230,310,313,316) (ORF32 and ORF19 respectively in RRV/KSHV). We hypothesized that, as an inner tegument protein, ORF52 may be in proximity to interact with ORF32 and/or ORF19 and that, with it absent in the kd conditions, the DNA may not be as securely packaged.…”

Section: Release Of Subviral Particles In Orf52 Kdmentioning

confidence: 99%

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Role of RRV ORF52 in Virion Maturation

Anderson¹

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Rhesus monkey rhadinovirus (RRV) is a close relative of the human pathogen, Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Primary infection with KSHV in culture is highly inefficient and it predominantly adopts a latent phenotype, expressing only a minimal number of viral genes and producing no progeny virions. This contrasts with RRV in culture, which replicates to high viral titer and produces abundant progeny virions, making it a useful model to study gammaherpesvirus lytic replication, virion structure, and the potential roles of tegument proteins in the biology of gammaherpesviruses. Initial work in our laboratory determined that the RRV virion was composed of 33 virally encoded proteins. Of these, 17 are tegument proteins, five of which are unique to the gammaherpesvirus subfamily. ORF52 is one of these five gammaherpesvirus specific tegument proteins and is the focus of this dissertation. This protein is highly abundant within the virion (approximately 1000 copies per particle) and it is closely associated with the capsid. Our results describe a critical role for ORF52 in the cytoplasmic-based later stages of virion morphogenesis. Without ORF52, capsids fail to undergo tegumentation, which is necessary for final envelopment and production of fully infectious virions. In a later section of this dissertation, we also describe preliminary data proposing that ORF52 may play a direct or indirect role in virion transport through interaction with cellular microtubules.iii ACKNOWLEDGEMENTS I grew up in a small, blue-collar, southern Illinois town where most people stay local and focus on getting by day-to-day, not on things like big cities and advanced degrees. I didn't even know what "graduate school" was until several years into my undergraduate education in Chicago, which, by the way, took me 9 years to complete because I worked full-time and went to school off-and-on and part-time when time and money permitted. The reason I share this is because I didn't get here alone, I didn't even know where "here" was and if I'm honest, I don't think I ever really believed I would earn a PhD, because where I'm from, things like that just don't happen to people like me. There truly are so many people I am honored to thank for helping, and supporting, me at various points in this long, wonderful, horrible, amazing, and trying journey that has been the last 10 years of my life, 7 of those at UVa.

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Virus Assembly

Rowlands¹,

Stockley²

2016

Encyclopedia of Life Sciences

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Viral genomes are sequestered by capsid proteins to form nucleocapsids with icosahedral (pseudospherical) or helical symmetry. Mature virus particles (virions) may be naked (i.e. composed of nucleic acid and protein only) or enveloped within a lipid bilayer(s). There is great diversity in size and complexity across the virus spectrum; recently discovered giant viruses are larger than some bacteria. Virions assemble from relatively large numbers of a few identical subunits but may include additional proteins required for specialised functions. Various mechanisms ensure that only viral genomic nucleic acids are packaged. Virion components are transported by cellular processes to sites of assembly. Basic functions of virions are protection of the genome from environmental damage during extracellular existence and delivery to a susceptible cell to initiate a new infection. Proteolytic cleavage of specific proteins during virus maturation commonly induces a quasi‐stable ‘triggered’ state to allow conformational changes necessary for cell penetration and genome release. Key Concepts For genetic economy, virions are assembled from large numbers of a few components. Nucleocapsids comprise the viral genomic nucleic acid sequestered within a protein coat. The symmetry of nucleocapsids is usually icosahedral or helical. Virions are either nonenveloped (i.e. a naked nucleocapsid) or enveloped by a lipid membrane. Virus‐specific nucleic acids are selectively packaged within nucleocapsids. Intracellular transport mechanisms are hijacked by viruses to ensure that components are delivered to sites of assembly. Postassembly proteolytic cleavages are often used to induce a quasi‐stable state primed for cell entry.

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Allosteric Signaling and a Nuclear Exit Strategy: Binding of UL25/UL17 Heterodimers to DNA-Filled HSV-1 Capsids

Cited by 155 publications

References 47 publications

Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM

Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM

Role of RRV ORF52 in Virion Maturation

Virus Assembly

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