PDBsum entry 3d11

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Hydrolase PDB id
Protein chain
427 a.a. *
IOD ×19
Waters ×210
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structures of the nipah g attachment glycoprotein
Structure: Hemagglutinin-neuraminidase. Chain: a. Fragment: unp residues 176-602. Engineered: yes
Source: Nipah virus. Organism_taxid: 121791. Gene: hn. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
2.31Å     R-factor:   0.228     R-free:   0.257
Authors: K.Xu,K.R.Rajashankar,Y.P.Chan,P.Himanen,C.C.Broder,D.B.Nikol
Key ref:
K.Xu et al. (2008). Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3. Proc Natl Acad Sci U S A, 105, 9953-9958. PubMed id: 18632560 DOI: 10.1073/pnas.0804797105
02-May-08     Release date:   19-Aug-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9IH62  (GLYCP_NIPAV) -  Glycoprotein G
602 a.a.
427 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     viral envelope   1 term 
  Biological process     viral infectious cycle   1 term 
  Biochemical function     host cell surface receptor binding     2 terms  


DOI no: 10.1073/pnas.0804797105 Proc Natl Acad Sci U S A 105:9953-9958 (2008)
PubMed id: 18632560  
Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3.
K.Xu, K.R.Rajashankar, Y.P.Chan, J.P.Himanen, C.C.Broder, D.B.Nikolov.
Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound state and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G beta-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.
  Selected figure(s)  
Figure 2.
Crystal structure of the NiV-G/ephrin-B3 complex. (A) Side view of the NiV-G/ephrin-B3 complex. The β-strands of NiV-G are colored in magenta, and the α-helices are in cyan. The β-strands of ephrin-B3 are colored in yellow and the α-helices are in red. The carbohydrate moieties, shown as stick models, do not interact with ephrin-B3 but extend in the solvent. The N and C termini of the molecules are labeled. (B) The molecular surfaces of the henipavirus (cyan) and the parainfluenza virus (magenta) attachment proteins along the top (or receptor-binding) face of the molecules. The lower images are close-up views of the receptor-binding pockets with the bound receptor (ephrin-B3 G–H loop in yellow, sialic acid in green). Only the G–H loop of ephrin-B3 is shown. In red are shown the NiV-G residues that interact with ephrin-B3 residues outside of the G–H loop, highlighting the polar region of the NiV-G/ephrin interface.
Figure 5.
Structure of the NiV-G/ephrin interface. Interacting residues are labeled. (A) Salt bridges at the polar (peripheral) region of the NiV-G/ephrin interface. NiV-G is in yellow and ephrin-B3 in gray. (B) The G–H ephrin-B3 loop bound to the NiV-G surface channel. (C) The same surface in the unbound NiV-G molecule. The position of the G–H ephrin-B3 loop is still shown to illustrate that the binding pockets for ephrin residues P122, L124, and W125 are already fully formed in the unbound attachment protein and undergo little or no conformational rearrangements upon ephrin binding. On the other hand, the Y120 binding pocket is only formed upon ephrin binding.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21217702 T.Hashiguchi, T.Ose, M.Kubota, N.Maita, J.Kamishikiryo, K.Maenaka, and Y.Yanagi (2011).
Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM.
  Nat Struct Mol Biol, 18, 135-141.
PDB codes: 3alw 3alx 3alz
20010840 C.Santiago, M.L.Celma, T.Stehle, and J.M.Casasnovas (2010).
Structure of the measles virus hemagglutinin bound to the CD46 receptor.
  Nat Struct Mol Biol, 17, 124-129.
PDB code: 3inb
  21073718 D.Khetawat, and C.C.Broder (2010).
A functional henipavirus envelope glycoprotein pseudotyped lentivirus assay system.
  Virol J, 7, 312.  
20519383 H.C.Aguilar, V.Aspericueta, L.R.Robinson, K.E.Aanensen, and B.Lee (2010).
A quantitative and kinetic fusion protein-triggering assay can discern distinct steps in the nipah virus membrane fusion cascade.
  J Virol, 84, 8033-8041.  
20585631 R.E.Dutch (2010).
Entry and fusion of emerging paramyxoviruses.
  PLoS Pathog, 6, e1000881.  
20375167 T.A.Bowden, M.Crispin, D.J.Harvey, E.Y.Jones, and D.I.Stuart (2010).
Dimeric architecture of the Hendra virus attachment glycoprotein: evidence for a conserved mode of assembly.
  J Virol, 84, 6208-6217.
PDB code: 2x9m
19878307 E.C.Smith, A.Popa, A.Chang, C.Masante, and R.E.Dutch (2009).
Viral entry mechanisms: the increasing diversity of paramyxovirus entry.
  FEBS J, 276, 7217-7227.  
19019819 H.C.Aguilar, Z.A.Ataman, V.Aspericueta, A.Q.Fang, M.Stroud, O.A.Negrete, R.A.Kammerer, and B.Lee (2009).
A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F).
  J Biol Chem, 284, 1628-1635.  
19525919 J.P.Himanen, Y.Goldgur, H.Miao, E.Myshkin, H.Guo, M.Buck, M.Nguyen, K.R.Rajashankar, B.Wang, and D.B.Nikolov (2009).
Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex.
  EMBO Rep, 10, 722-728.
PDB codes: 3hei 3hpn
19888339 K.N.Bossart, Z.Zhu, D.Middleton, J.Klippel, G.Crameri, J.Bingham, J.A.McEachern, D.Green, T.J.Hancock, Y.P.Chan, A.C.Hickey, D.S.Dimitrov, L.F.Wang, and C.C.Broder (2009).
A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.
  PLoS Pathog, 5, e1000642.  
  19901337 K.Wu, W.Li, G.Peng, and F.Li (2009).
Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor.
  Proc Natl Acad Sci U S A, 106, 19970-19974.
PDB code: 3kbh
19216624 P.Prabakaran, Z.Zhu, X.Xiao, A.Biragyn, A.S.Dimitrov, C.C.Broder, and D.S.Dimitrov (2009).
Potent human monoclonal antibodies against SARS CoV, Nipah and Hendra viruses.
  Expert Opin Biol Ther, 9, 355-368.  
  20161127 R.M.Iorio, V.R.Melanson, and P.J.Mahon (2009).
Glycoprotein interactions in paramyxovirus fusion.
  Future Virol, 4, 335-351.  
19710150 S.A.Connolly, G.P.Leser, T.S.Jardetzky, and R.A.Lamb (2009).
Bimolecular complementation of paramyxovirus fusion and hemagglutinin-neuraminidase proteins enhances fusion: implications for the mechanism of fusion triggering.
  J Virol, 83, 10857-10868.  
19656895 T.Paal, M.A.Brindley, C.St Clair, A.Prussia, D.Gaus, S.A.Krumm, J.P.Snyder, and R.K.Plemper (2009).
Probing the spatial organization of measles virus fusion complexes.
  J Virol, 83, 10480-10493.  
19342221 T.Stehle, and J.M.Casasnovas (2009).
Specificity switching in virus-receptor complexes.
  Curr Opin Struct Biol, 19, 181-188.  
  19193989 Y.Goldgur, S.Paavilainen, D.Nikolov, and J.P.Himanen (2009).
Structure of the ligand-binding domain of the EphB2 receptor at 2 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 71-74.
PDB code: 3etp
18799571 K.A.Bishop, A.C.Hickey, D.Khetawat, J.R.Patch, K.N.Bossart, Z.Zhu, L.F.Wang, D.S.Dimitrov, and C.C.Broder (2008).
Residues in the stalk domain of the hendra virus g glycoprotein modulate conformational changes associated with receptor binding.
  J Virol, 82, 11398-11409.  
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.