Cryo-EM structure of a herpesvirus capsid at 3.1 Å

Science ◽  
2018 ◽  
Vol 360 (6384) ◽  
pp. eaao7283 ◽  
Author(s):  
Shuai Yuan ◽  
Jialing Wang ◽  
Dongjie Zhu ◽  
Nan Wang ◽  
Qiang Gao ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Disulfide Bonds ◽  
Major Capsid Protein ◽  
Noncovalent Interactions ◽  
Cryo Electron Microscopy ◽  
Reconstruction Strategy ◽  
Simplex Virus ◽  
Capsid Stability ◽  
Human Herpesviruses

Structurally and genetically, human herpesviruses are among the largest and most complex of viruses. Using cryo–electron microscopy (cryo-EM) with an optimized image reconstruction strategy, we report the herpes simplex virus type 2 (HSV-2) capsid structure at 3.1 angstroms, which is built up of about 3000 proteins organized into three types of hexons (central, peripentonal, and edge), pentons, and triplexes. Both hexons and pentons contain the major capsid protein, VP5; hexons also contain a small capsid protein, VP26; and triplexes comprise VP23 and VP19C. Acting as core organizers, VP5 proteins form extensive intermolecular networks, involving multiple disulfide bonds (about 1500 in total) and noncovalent interactions, with VP26 proteins and triplexes that underpin capsid stability and assembly. Conformational adaptations of these proteins induced by their microenvironments lead to 46 different conformers that assemble into a massive quasisymmetric shell, exemplifying the structural and functional complexity of HSV.

scholarly journals CD4 T-Cell Responses to Herpes Simplex Virus Type 2 Major Capsid Protein VP5: Comparison with Responses to Tegument and Envelope Glycoproteins

2000 ◽  
Vol 74 (23) ◽  
pp. 11422-11425 ◽  
Author(s):  
David M. Koelle ◽  
Mark Schomogyi ◽  
Christopher McClurkan ◽  
Sigrid N. Reymond ◽  
Hongbo B. Chen
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Capsid Protein ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Major Capsid Protein ◽  
Cd4 Lymphocyte ◽  
Simplex Virus

ABSTRACT We used CD4 lymphocyte clones from herpes simplex virus type 2 (HSV-2) lesions or the cervix and molecular libraries of HSV-2 DNA to define HSV-2 major capsid protein VP5 and glycoprotein E (gE) as T-cell antigens. Responses to eight HSV-2 glycoprotein, tegument, nonstructural, or capsid antigens were compared in 19 donors. Recognition of VP5 and tegument VP22 were similar to that of gB2 and gD2, currently under study as vaccines. These prevalence data suggest that HSV capsid and tegument proteins may also be candidate vaccine antigens.

Architecture of the Herpes Simplex Virus Major Capsid Protein Derived from Structural Bioinformatics

2003 ◽  
Vol 331 (2) ◽  
pp. 447-456 ◽  
Author(s):  
Matthew L. Baker ◽  
Wen Jiang ◽  
Brian R. Bowman ◽  
Z. Hong Zhou ◽  
Florante A. Quiocho ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Capsid Protein ◽  
Major Capsid Protein ◽  
Structural Bioinformatics ◽  
Simplex Virus

scholarly journals Three-Dimensional Localization of the Smallest Capsid Protein in the Human Cytomegalovirus Capsid

2005 ◽  
Vol 79 (2) ◽  
pp. 1327-1332 ◽  
Author(s):  
Xuekui Yu ◽  
Sanket Shah ◽  
Ivo Atanasov ◽  
Pierrette Lo ◽  
Fenyong Liu ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Human Cytomegalovirus ◽  
Major Capsid Protein ◽  
Three Dimensional ◽  
Oligomeric State ◽  
Sequence Structure ◽  
Protein Subunits ◽  
And Function ◽  
Antibody Labeling ◽  
Human Herpesviruses

ABSTRACT The smallest capsid proteins (SCPs) of the human herpesviruses differ substantially in size and sequence and are thought to impart some unique aspects of infection to their respective viruses. We used electron cryomicroscopy and antibody labeling to show that the 8-kDa SCP of human cytomegalovirus is attached only to major capsid protein subunits of the hexons, not the pentons. Thus, the SCPs of different herpesviruses illustrate that a protein can evolve significantly in sequence, structure, and function, while preserving its role in the architecture of the virus by binding to a specific partner in a specific oligomeric state.

scholarly journals Assembly of the Herpes Simplex Virus Procapsid from Purified Components and Identification of Small Complexes Containing the Major Capsid and Scaffolding Proteins

1999 ◽  
Vol 73 (5) ◽  
pp. 4239-4250 ◽  
Author(s):  
William W. Newcomb ◽  
Fred L. Homa ◽  
Darrell R. Thomsen ◽  
Benes L. Trus ◽  
Naiqian Cheng ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Capsid Protein ◽  
Major Capsid Protein ◽  
Scaffolding Protein ◽  
Oligomeric State ◽  
Cell Extracts ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT An in vitro system is described for the assembly of herpes simplex virus type 1 (HSV-1) procapsids beginning with three purified components, the major capsid protein (VP5), the triplexes (VP19C plus VP23), and a hybrid scaffolding protein. Each component was purified from insect cells expressing the relevant protein(s) from an appropriate recombinant baculovirus vector. Procapsids formed when the three purified components were mixed and incubated for 1 h at 37°C. Procapsids assembled in this way were found to be similar in morphology and in protein composition to procapsids formed in vitro from cell extracts containing HSV-1 proteins. When scaffolding and triplex proteins were present in excess in the purified system, greater than 80% of the major capsid protein was incorporated into procapsids. Sucrose density gradient ultracentrifugation studies were carried out to examine the oligomeric state of the purified assembly components. These analyses showed that (i) VP5 migrated as a monomer at all of the protein concentrations tested (0.1 to 1 mg/ml), (ii) VP19C and VP23 migrated together as a complex with the same heterotrimeric composition (VP19C1-VP232) as virus triplexes, and (iii) the scaffolding protein migrated as a heterogeneous mixture of oligomers (in the range of monomers to ∼30-mers) whose composition was strongly influenced by protein concentration. Similar sucrose gradient analyses performed with mixtures of VP5 and the scaffolding protein demonstrated the presence of complexes of the two having molecular weights in the range of 200,000 to 600,000. The complexes were interpreted to contain one or two VP5 molecules and up to six scaffolding protein molecules. The results suggest that procapsid assembly may proceed by addition of the latter complexes to regions of growing procapsid shell. They indicate further that procapsids can be formed in vitro from virus-encoded proteins only without any requirement for cell proteins.

scholarly journals The 4.4 Å structure of the giant Melbournevirus virion belonging to the Marseilleviridae family

2021 ◽  
Author(s):  
Raymond N Burton-Smith ◽  
Hemanth K N Reddy ◽  
Martin Svenda ◽  
Chantal Abergel ◽  
Kenta Okamoto ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Capsid Protein ◽  
Major Capsid Protein ◽  
Capsid Proteins ◽  
Atomic Model ◽  
Penton Base ◽  
Cryo Electron Microscopy ◽  
Internal Membrane ◽  
Structural Details ◽  
Giant Viruses

Members of Marseilleviridae, one family of icosahedral giant viruses classified in 2012 have been identified worldwide in all types of environments. The virion shows a characteristic internal membrane extrusion at the five-fold vertices of the capsid, but its structural details need to be elucidated. We now report the 4.4 Å cryo-electron microscopy structure of the Melbournevirus capsid. An atomic model of the major capsid protein (MCP) shows a unique cup structure on the trimer that accommodates additional proteins. A polyalanine model of the penton base protein shows internally extended N- and C-terminals, which indirectly connect to the internal membrane extrusion. The Marseilleviruses share the same orientational organisation of the MCPs as PBCV-1 and CroV, but do not appear to possess a protein akin to the ″tape measure″ of these viruses. Minor capsid proteins named PC-β, zipper, and scaffold are proposed to control the dimensions of the capsid during assembly.

scholarly journals The UL14 protein of herpes simplex virus type 2 translocates the minor capsid protein VP26 and the DNA cleavage and packaging UL33 protein into the nucleus of coexpressing cells

2001 ◽  
Vol 82 (2) ◽  
pp. 321-330 ◽  
Author(s):  
Yohei Yamauchi ◽  
Kaoru Wada ◽  
Fumi Goshima ◽  
Hiroki Takakuwa ◽  
Tohru Daikoku ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Capsid Protein ◽  
Herpes Simplex Virus Type ◽  
Dna Cleavage ◽  
Mutual Influence ◽  
Intracellular Localization ◽  
Minor Capsid Protein ◽  
Simplex Virus

The herpes simplex virus type 2 (HSV-2) gene UL14 encodes a 32 kDa protein which is a minor component of the virion tegument and is expressed late in infection. The UL14 protein shows varied localization patterns in HSV-2-infected and singly expressing cells, suggesting the possibility that it is multifunctional. We have investigated the influence of the UL14 protein on the intracellular localization of capsid proteins and DNA cleavage and packaging proteins in coexpressing cells. VP26 is the minor capsid protein; it binds to hexons of the outer capsid shell and is predominantly cytoplasmic upon sole expression. We have found that VP26 coexpressed with the UL14 protein showed mutual and predominant relocation into the nucleus. At least seven viral genes encode proteins (UL6, UL15, UL17, UL25, UL28, UL32 and UL33) that are required for DNA cleavage and packaging. We have found that the UL33 protein, which was also cytoplasmic by sole expression, was relocated to the nucleus upon expression with the UL14 protein, which again seemed to be a result of mutual influence. Coexpression experiments also suggested the possibility of a mutual influence between the UL14 and UL17 proteins, and the UL17 protein and VP26. Our results suggest that the UL14 protein can influence the intracellular localization patterns of a number of proteins belonging to the capsid or the DNA encapsidation machinery.

scholarly journals Capsid Structure of Simian Cytomegalovirus from Cryoelectron Microscopy: Evidence for Tegument Attachment Sites

1999 ◽  
Vol 73 (3) ◽  
pp. 2181-2192 ◽  
Author(s):  
Benes L. Trus ◽  
Wade Gibson ◽  
Naiqian Cheng ◽  
Alasdair C. Steven
Keyword(s):  
Capsid Protein ◽  
Major Capsid Protein ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Cryoelectron Microscopy ◽  
Tegument Proteins ◽  
Attachment Sites ◽  
The Matrix ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT We have used cryoelectron microscopy and image reconstruction to study B-capsids recovered from both the nuclear and the cytoplasmic fractions of cells infected with simian cytomegalovirus (SCMV). SCMV, a representative betaherpesvirus, could thus be compared with the previously described B-capsids of the alphaherpesviruses, herpes simplex virus type 1 (HSV-1) and equine herpesvirus 1 (EHV-1), and of channel catfish virus, an evolutionarily remote herpesvirus. Nuclear B-capsid architecture is generally conserved with SCMV, but it is 4% larger in inner radius than HSV-1, implying that its ∼30% larger genome should be packed more tightly. Isolated SCMV B-capsids retain a relatively well preserved inner shell (or “small core”) of scaffolding-assembly protein, whose radial-density profile indicates that this protein is ∼16-nm long and consists of two domains connected by a low-density linker. As with HSV-1, the hexons but not the pentons of the major capsid protein (151 kDa) bind the smallest capsid protein (∼8 kDa). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed cytoplasmic B-capsid preparations to contain proteins similar in molecular weight to the basic phosphoprotein (∼119 kDa) and the matrix proteins (65 to 70 kDa). Micrographs revealed that these particles had variable amounts of surface-adherent material not present on nuclear B-capsids that we take to be tegument proteins. Cytoplasmic B-capsids were classified accordingly as lightly, moderately, or heavily tegumented. By comparing the three corresponding density maps with each other and with the nuclear B-capsid, two interactions were identified between putative tegument proteins and the capsid surface. One is between the major capsid protein and a protein estimated by electron microscopy to be 50 to 60 kDa; the other involves an elongated molecule estimated to be 100 to 120 kDa that is anchored on the triplexes, most likely on its dimer subunits. Candidates for the proteins bound at these sites are discussed. This first visualization of such linkages makes a step towards understanding the organization and functional rationale of the herpesvirus tegument.

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