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PDBsum entry 3c6e
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protein ligands Protein-protein interface(s) links
Viral protein PDB id
3c6e

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
390 a.a.
81 a.a.
Ligands
NAG-NDG-MAN-MAN
NDG
NAG
Waters ×45
PDB id:
3c6e
Name: Viral protein
Title: Crystal structure of the precursor membrane protein- envelope protein heterodimer from the dengue 2 virus at neutral ph
Structure: Envelope protein e. Chain: a. Fragment: unp residues 281-674. Engineered: yes. Prm. Chain: c. Fragment: unp residues 115-244. Engineered: yes
Source: Dengue virus 2 thailand/16681/84. Organism_taxid: 31634. Strain: 16681. Expressed in: drosophila. Expression_system_taxid: 7215. Dengue virus. Organism_taxid: 11060. Strain: 2.
Resolution:
2.60Å     R-factor:   0.250     R-free:   0.293
Authors: L.Li
Key ref:
L.Li et al. (2008). The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science, 319, 1830-1834. PubMed id: 18369147 DOI: 10.1126/science.1153263
Date:
04-Feb-08     Release date:   08-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O11875  (O11875_9FLAV) -  Genome polyprotein from dengue virus type 2
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		3391 a.a.
390 a.a.*
Protein chain
Pfam   ArchSchema ?
Q3BCY3  (Q3BCY3_9FLAV) -  Genome polyprotein (Fragment) from dengue virus type 2
Seq:
Struc: 		 
Seq:
Struc: 		661 a.a.
81 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 2: Chain A: E.C.3.4.21.91  - flavivirin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Selective hydrolysis of Xaa-Xaa-|-Xbb bonds in which each of the Xaa can be either Arg or Lys and Xbb can be either Ser or Ala.
   Enzyme class 3: Chain A: E.C.3.6.1.15  - nucleoside-triphosphate phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H+
ribonucleoside 5'-triphosphate
 + H2O
 = ribonucleoside 5'-diphosphate
 + phosphate
 + H(+)
   Enzyme class 4: Chain A: E.C.3.6.4.13  - Rna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
 + H2O
 =
ADP
Bound ligand (Het Group name = NAG)
matches with 41.38% similarity 		+ phosphate
 + H(+)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1126/science.1153263 Science 319:1830-1834 (2008)
PubMed id: 18369147  
 
 
The flavivirus precursor membrane-envelope protein complex: structure and maturation.
L.Li, S.M.Lok, I.M.Yu, Y.Zhang, R.J.Kuhn, J.Chen, M.G.Rossmann.
 
  ABSTRACT  
 
Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide beta-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Rearrangement of the prM and E proteins during virus maturation. (A to D) Sequence of events as referenced in the text. The E proteins are shown as a C backbone; space-filling atoms show the pr peptide surfaces. The three independent heterodimers per icosahedral asymmetric unit are colored red, green, and blue. Although the diagram assumes knowledge of the relationship among the positions of specific heterodimers in the immature and mature viruses (red goes to red, green to green, and blue to blue), this is not known. 		Figure 3.
Fig. 3. Structure of the prM-E protein. (A)Stereoview of the prM-E heterodimer in ribbon representation. The pr peptide is cyan, DI is red, DII is yellow, DIII is blue, and the fusion loop is green. Secondary structural elements of the E protein are labeled (7, 21). Secondary structural elements for the pr peptide are defined here as a[pr], b[pr], ···, g[pr]. (B) Secondary structure of the pr peptide. Disulfide linkages are indicated with dashed lines. (C) Open-book view of the pr-E interactions showing charge complementarity. Positively and negatively charged surfaces in the contact areas are colored blue and red, respectively. Charged residues in the contact area are labeled. The fusion loop (residues 100 to 108) is outlined in green. Contact areas are defined by atoms less than 4.5 Å apart between the pr peptide and the E protein (21).
 
  The above figures are reprinted by permission from the AAAs: Science (2008, 319, 1830-1834) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23241927 X.Zhang, P.Ge, X.Yu, J.M.Brannan, G.Bi, Q.Zhang, S.Schein, and Z.H.Zhou (2013).
Cryo-EM structure of the mature dengue virus at 3.5-Å resolution.
  Nat Struct Mol Biol, 20, 105-110.
PDB codes: 3j27 3j2p
21388812 I.A.Rodenhuis-Zybert, J.Wilschut, and J.M.Smit (2011).
Partial maturation: an immune-evasion strategy of dengue virus?
  Trends Microbiol, 19, 248-254.  
20386713 A.G.Schmidt, P.L.Yang, and S.C.Harrison (2010).
Peptide inhibitors of dengue-virus entry target a late-stage fusion intermediate.
  PLoS Pathog, 6, e1000851.  
20975939 A.Zheng, M.Umashankar, and M.Kielian (2010).
In vitro and in vivo studies identify important features of dengue virus pr-E protein interactions.
  PLoS Pathog, 6, e1001157.  
20369024 B.Shrestha, J.D.Brien, S.Sukupolvi-Petty, S.K.Austin, M.A.Edeling, T.Kim, K.M.O'Brien, C.A.Nelson, S.Johnson, D.H.Fremont, and M.S.Diamond (2010).
The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1.
  PLoS Pathog, 6, e1000823.  
20519400 J.Junjhon, T.J.Edwards, U.Utaipat, V.D.Bowman, H.A.Holdaway, W.Zhang, P.Keelapang, C.Puttikhunt, R.Perera, P.R.Chipman, W.Kasinrerk, P.Malasit, R.J.Kuhn, and N.Sittisombut (2010).
Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles.
  J Virol, 84, 8353-8358.  
21124457 L.Li, J.Jose, Y.Xiang, R.J.Kuhn, and M.G.Rossmann (2010).
Structural changes of envelope proteins during alphavirus fusion.
  Nature, 468, 705-708.
PDB codes: 3muu 3muw
20335260 M.Liao, C.Sánchez-San Martín, A.Zheng, and M.Kielian (2010).
In vitro reconstitution reveals key intermediate states of trimer formation by the dengue virus membrane fusion protein.
  J Virol, 84, 5730-5740.  
20550721 R.A.Gadkari, and N.Srinivasan (2010).
Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures.
  BMC Struct Biol, 10, 17.  
20592088 S.Sukupolvi-Petty, S.K.Austin, M.Engle, J.D.Brien, K.A.Dowd, K.L.Williams, S.Johnson, R.Rico-Hesse, E.Harris, T.C.Pierson, D.H.Fremont, and M.S.Diamond (2010).
Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2.
  J Virol, 84, 9227-9239.  
20660783 T.Matsui, G.C.Lander, R.Khayat, and J.E.Johnson (2010).
Subunits fold at position-dependent rates during maturation of a eukaryotic RNA virus.
  Proc Natl Acad Sci U S A, 107, 14111-14115.  
20448183 W.Dejnirattisai, A.Jumnainsong, N.Onsirisakul, P.Fitton, S.Vasanawathana, W.Limpitikul, C.Puttikhunt, C.Edwards, T.Duangchinda, S.Supasa, K.Chawansuntati, P.Malasit, J.Mongkolsapaya, and G.Screaton (2010).
Cross-reacting antibodies enhance dengue virus infection in humans.
  Science, 328, 745-748.  
18796313 A.Sampath, and R.Padmanabhan (2009).
Molecular targets for flavivirus drug discovery.
  Antiviral Res, 81, 6.  
  20165556 B.J.Geiss, H.Stahla, A.M.Hannah, H.H.Gari, and S.M.Keenan (2009).
Focus on flaviviruses: current and future drug targets.
  Future Med Chem, 1, 327.  
19796949 C.Sánchez-San Martín, C.Y.Liu, and M.Kielian (2009).
Dealing with low pH: entry and exit of alphaviruses and flaviviruses.
  Trends Microbiol, 17, 514-521.  
19759134 I.M.Yu, H.A.Holdaway, P.R.Chipman, R.J.Kuhn, M.G.Rossmann, and J.Chen (2009).
Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion.
  J Virol, 83, 12101-12107.
PDB code: 3iya
19380111 M.D.Fernandez-Garcia, M.Mazzon, M.Jacobs, and A.Amara (2009).
Pathogenesis of flavivirus infections: using and abusing the host cell.
  Cell Host Microbe, 5, 318-328.  
19386704 M.R.Vogt, B.Moesker, J.Goudsmit, M.Jongeneelen, S.K.Austin, T.Oliphant, S.Nelson, T.C.Pierson, J.Wilschut, M.Throsby, and M.S.Diamond (2009).
Human monoclonal antibodies against West Nile virus induced by natural infection neutralize at a postattachment step.
  J Virol, 83, 6494-6507.  
19713934 M.V.Cherrier, B.Kaufmann, G.E.Nybakken, S.M.Lok, J.T.Warren, B.R.Chen, C.A.Nelson, V.A.Kostyuchenko, H.A.Holdaway, P.R.Chipman, R.J.Kuhn, M.S.Diamond, M.G.Rossmann, and D.H.Fremont (2009).
Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody.
  EMBO J, 28, 3269-3276.
PDB codes: 3i50 3ixx 3ixy
18996430 N.Bonafé, J.A.Rininger, R.G.Chubet, H.G.Foellmer, S.Fader, J.F.Anderson, S.L.Bushmich, K.Anthony, M.Ledizet, E.Fikrig, R.A.Koski, and P.Kaplan (2009).
A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells.
  Vaccine, 27, 213-222.  
20016834 P.G.Wang, M.Kudelko, J.Lo, L.Y.Siu, K.T.Kwok, M.Sachse, J.M.Nicholls, R.Bruzzone, R.M.Altmeyer, and B.Nal (2009).
Efficient assembly and secretion of recombinant subviral particles of the four dengue serotypes using native prM and E proteins.
  PLoS One, 4, e8325.  
19439655 R.V.Mannige, and C.L.Brooks (2009).
Geometric considerations in virus capsid size specificity, auxiliary requirements, and buckling.
  Proc Natl Acad Sci U S A, 106, 8531-8536.  
20365004 S.B.Rochal, and V.L.Lorman (2009).
Theory of a reconstructive structural transformation in capsids of icosahedral viruses.
  Phys Rev E Stat Nonlin Soft Matter Phys, 80, 051905.  
19264649 T.T.Tan, R.Bhuvanakantham, J.Li, J.Howe, and M.L.Ng (2009).
Tyrosine 78 of premembrane protein is essential for assembly of West Nile virus.
  J Gen Virol, 90, 1081-1092.  
19244325 Z.L.Qin, Y.Zheng, and M.Kielian (2009).
Role of conserved histidine residues in the low-pH dependence of the Semliki Forest virus fusion protein.
  J Virol, 83, 4670-4677.  
  19064260 C.Sánchez-San Martín, H.Sosa, and M.Kielian (2008).
A stable prefusion intermediate of the alphavirus fusion protein reveals critical features of class II membrane fusion.
  Cell Host Microbe, 4, 600-608.  
18758509 J.Basque, M.Martel, R.Leduc, and A.M.Cantin (2008).
Lysosomotropic drugs inhibit maturation of transforming growth factor-beta.
  Can J Physiol Pharmacol, 86, 606-612.  
18936253 R.Fritz, K.Stiasny, and F.X.Heinz (2008).
Identification of specific histidines as pH sensors in flavivirus membrane fusion.
  J Cell Biol, 183, 353-361.  
18585795 R.Perera, M.Khaliq, and R.J.Kuhn (2008).
Closing the door on flaviviruses: entry as a target for antiviral drug design.
  Antiviral Res, 80, 11-22.  
  18779049 T.C.Pierson, D.H.Fremont, R.J.Kuhn, and M.S.Diamond (2008).
Structural insights into the mechanisms of antibody-mediated neutralization of flavivirus infection: implications for vaccine development.
  Cell Host Microbe, 4, 229-238.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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