PDBsum entry 2zb5

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Viral protein PDB id
Jmol PyMol
Protein chain
424 a.a.
NAG ×2
PDB id:
Name: Viral protein
Title: Crystal structure of the measles virus hemagglutinin (comple type)
Structure: Hemagglutinin protein. Chain: a. Fragment: head domain, unp residues 149-617. Engineered: yes. Mutation: yes
Source: Measles virus strain edmonston-b. Organism_taxid: 70146. Strain: edmonston b. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Expression_system_organ: kidney.
3.00Å     R-factor:   0.227     R-free:   0.271
Authors: T.Hashiguchi,M.Kajikawa,N.Maita,M.Takeda,K.Kuroki,K.Sasaki,D Y.Yanagi,K.Maenaka
Key ref:
T.Hashiguchi et al. (2007). Crystal structure of measles virus hemagglutinin provides insight into effective vaccines. Proc Natl Acad Sci U S A, 104, 19535-19540. PubMed id: 18003910 DOI: 10.1073/pnas.0707830104
16-Oct-07     Release date:   06-Nov-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08362  (HEMA_MEASE) -  Hemagglutinin glycoprotein
617 a.a.
424 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 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     1 term  


DOI no: 10.1073/pnas.0707830104 Proc Natl Acad Sci U S A 104:19535-19540 (2007)
PubMed id: 18003910  
Crystal structure of measles virus hemagglutinin provides insight into effective vaccines.
T.Hashiguchi, M.Kajikawa, N.Maita, M.Takeda, K.Kuroki, K.Sasaki, D.Kohda, Y.Yanagi, K.Maenaka.
Measles still remains a major cause of childhood morbidity and mortality worldwide. Measles virus (MV) vaccines are highly successful, but the mechanism underlying their efficacy has been unclear. Here we report the crystal structure of the MV attachment protein, hemagglutinin, responsible for MV entry. The receptor-binding head domain exhibits a cubic-shaped beta-propeller structure and forms a homodimer. N-linked sugars appear to mask the broad regions and cause the two molecules forming the dimer to tilt oppositely toward the horizontal plane. Accordingly, residues of the putative receptor-binding site, highly conserved among MV strains, are strategically positioned in the unshielded area of the protein. These conserved residues also serve as epitopes for neutralizing antibodies, ensuring the serological monotype, a basis for effective MV vaccines. Our findings suggest that sugar moieties in the MV hemagglutinin critically modulate virus-receptor interaction as well as antiviral antibody responses, differently from sugars of the HIV gp120, which allow for immune evasion.
  Selected figure(s)  
Figure 3.
Fig. 3. The receptor-binding sites of MV-H protein. (A) Putative SLAM-binding site. Electrostatic representation (Left) and ribbon-and-stick model (Right; at the same angle as Left) of the putative SLAM-binding site located on the loops of the β5 sheet. Red and blue surfaces indicate negatively and positively charged areas, respectively. The residues predicted by mutagenesis studies (23, 24) to be involved in SLAM binding are indicated in white stick models. The acidic residues comprising the "acidic patch" of the putative SLAM-binding site are shown in green stick models. (B) Putative SLAM- and CD46-binding sites on the MV-H structure: side (Left) and top (Right) views. The amino acid residues predicted to be involved in receptor binding (23, 24, 28) are shown in magenta (SLAM) and cyan/light blue (CD46, strong/weak effect). The color scheme used is the same as Fig. 1. (C) The conserved residues in H proteins of seven morbilliviruses (measles, rinderpest, peste-des-petits ruminants, canine distemper, dolphin distemper, porpoise distemper, and phocine distemper) are indicated on the MV-H protein. Red, identical; salmon, strong similarity; wheat, weak similarity; gray, little similarity. The residues of the putative SLAM-binding site (dotted circle) are strongly conserved.
Figure 4.
Fig. 4. Differential H/HN dimer formation and a schematic model of interactions between MV-H and its receptors. (A) Paramyxovirus (NDV, hPIV3, and SV5) HNs form dimers at a slight angle between monomers, whereas the MV-H dimer is tilted toward the horizontal plane to orient the receptor-binding sites upward. MV-H has sugar shield over the region corresponding to the active site in other paramyxoviruses. The cartoon model on the right is a representation of NDV. (B) A model of MV-H–receptor interaction. The putative SLAM- (red) and CD46- (blue) binding sites are oriented upward from the virus surface, easily accessible to the receptors. The N215-linked sugar shield (cyan circle) blocks any binding of the top pocket to antibodies, sialic acid, and other receptors. Additionally, the dimer and stalk interfaces, as well as the N-200-linked sugars, are not accessible.
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23202587 X.Zhang, G.Lu, J.Qi, Y.Li, Y.He, X.Xu, J.Shi, C.W.Zhang, J.Yan, and G.F.Gao (2013).
Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4.
  Nat Struct Mol Biol, 20, 67-72.
PDB code: 4gjt
21217701 C.K.Navaratnarajah, N.Oezguen, L.Rupp, L.Kay, V.H.Leonard, W.Braun, and R.Cattaneo (2011).
The heads of the measles virus attachment protein move to transmit the fusion-triggering signal.
  Nat Struct Mol Biol, 18, 128-134.  
21289649 E.O.Saphire, and M.B.Oldstone (2011).
Measles virus fusion shifts into gear.
  Nat Struct Mol Biol, 18, 115-116.  
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
  20057080 C.Santiago, A.Gutiérrez-Rodríguez, P.A.Tucker, T.Stehle, and J.M.Casasnovas (2010).
Crystallization and preliminary crystallographic analysis of the measles virus hemagglutinin in complex with the CD46 receptor.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 91-94.  
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
20636817 D.E.Griffin (2010).
Measles virus-induced suppression of immune responses.
  Immunol Rev, 236, 176-189.  
20631152 L.Zipperle, J.P.Langedijk, C.Orvell, M.Vandevelde, A.Zurbriggen, and P.Plattet (2010).
Identification of key residues in virulent canine distemper virus hemagglutinin that control CD150/SLAM-binding activity.
  J Virol, 84, 9618-9624.  
20702637 M.K.Ennis, C.Hu, S.K.Naik, L.K.Hallak, K.W.Peng, S.J.Russell, and D.Dingli (2010).
Mutations in the stalk region of the measles virus hemagglutinin inhibit syncytium formation but not virus entry.
  J Virol, 84, 10913-10917.  
19939927 P.B.Das, P.X.Dinh, I.H.Ansari, Lima, F.A.Osorio, and A.K.Pattnaik (2010).
The minor envelope glycoproteins GP2a and GP4 of porcine reproductive and respiratory syndrome virus interact with the receptor CD163.
  J Virol, 84, 1731-1740.  
20585633 R.Cattaneo (2010).
Paramyxovirus entry and targeted vectors for cancer therapy.
  PLoS Pathog, 6, e1000973.  
21221916 S.H.Ma, L.C.Wang, J.S.Liu, H.J.Shi, L.D.Liu, and Q.H.Li (2010).
Isolation and complete nucleotide sequence of the measles virus IMB-1 strain in China.
  Virol Sin, 25, 381-389.  
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
20053750 V.P.Mishin, M.Watanabe, G.Taylor, J.Devincenzo, M.Bose, A.Portner, and I.V.Alymova (2010).
N-linked glycan at residue 523 of human parainfluenza virus type 3 hemagglutinin-neuraminidase masks a second receptor-binding site.
  J Virol, 84, 3094-3100.  
19327858 C.J.Buchholz, M.D.Mühlebach, and K.Cichutek (2009).
Lentiviral vectors with measles virus glycoproteins - dream team for gene transfer?
  Trends Biotechnol, 27, 259-265.  
19013625 E.A.Corey, and R.M.Iorio (2009).
Measles virus attachment proteins with impaired ability to bind CD46 interact more efficiently with the homologous fusion protein.
  Virology, 383, 1-5.  
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.  
19553316 H.Okada, M.Itoh, K.Nagata, and K.Takeuchi (2009).
Previously unrecognized amino acid substitutions in the hemagglutinin and fusion proteins of measles virus modulate cell-cell fusion, hemadsorption, virus growth, and penetration rate.
  J Virol, 83, 8713-8721.  
19702505 N.Nair, W.J.Moss, S.Scott, N.Mugala, Z.M.Ndhlovu, K.Lilo, J.J.Ryon, M.Monze, T.C.Quinn, S.Cousens, F.Cutts, and D.E.Griffin (2009).
HIV-1 infection in Zambian children impairs the development and avidity maturation of measles virus-specific immunoglobulin G after vaccination and infection.
  J Infect Dis, 200, 1031-1038.  
  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.  
18523462 B.Lee, Z.A.Ataman, and L.Jin (2008).
Evil versus 'eph-ective' use of ephrin-B2.
  Nat Struct Mol Biol, 15, 540-542.  
18292085 C.K.Navaratnarajah, S.Vongpunsawad, N.Oezguen, T.Stehle, W.Braun, T.Hashiguchi, K.Maenaka, Y.Yanagi, and R.Cattaneo (2008).
Dynamic interaction of the measles virus hemagglutinin with its receptor signaling lymphocytic activation molecule (SLAM, CD150).
  J Biol Chem, 283, 11763-11771.  
18426797 J.K.Lee, A.Prussia, T.Paal, L.K.White, J.P.Snyder, and R.K.Plemper (2008).
Functional interaction between paramyxovirus fusion and attachment proteins.
  J Biol Chem, 283, 16561-16572.  
18786999 M.D.Mühlebach, V.H.Leonard, and R.Cattaneo (2008).
The measles virus fusion protein transmembrane region modulates availability of an active glycoprotein complex and fusion efficiency.
  J Virol, 82, 11437-11445.  
18287234 M.Tahara, M.Takeda, Y.Shirogane, T.Hashiguchi, S.Ohno, and Y.Yanagi (2008).
Measles virus infects both polarized epithelial and immune cells by using distinctive receptor-binding sites on its hemagglutinin.
  J Virol, 82, 4630-4637.  
18568081 M.Takeda (2008).
Measles virus breaks through epithelial cell barriers to achieve transmission.
  J Clin Invest, 118, 2386-2389.  
18552863 R.Cattaneo, T.Miest, E.V.Shashkova, and M.A.Barry (2008).
Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded.
  Nat Rev Microbiol, 6, 529-540.  
18346895 R.M.Iorio, and P.J.Mahon (2008).
Paramyxoviruses: different receptors - different mechanisms of fusion.
  Trends Microbiol, 16, 135-137.  
18488039 T.A.Bowden, A.R.Aricescu, R.J.Gilbert, J.M.Grimes, E.Y.Jones, and D.I.Stuart (2008).
Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2.
  Nat Struct Mol Biol, 15, 567-572.
PDB codes: 2vsk 2vsm
18815311 T.A.Bowden, M.Crispin, D.J.Harvey, A.R.Aricescu, J.M.Grimes, E.Y.Jones, and D.I.Stuart (2008).
Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design.
  J Virol, 82, 11628-11636.
PDB code: 2vwd
18568079 V.H.Leonard, P.L.Sinn, G.Hodge, T.Miest, P.Devaux, N.Oezguen, W.Braun, P.B.McCray, M.B.McChesney, and R.Cattaneo (2008).
Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed.
  J Clin Invest, 118, 2448-2458.  
18087048 R.W.Ruigrok, and D.Gerlier (2007).
Structure of the measles virus H glycoprotein sheds light on an efficient vaccine.
  Proc Natl Acad Sci U S A, 104, 20639-20640.  
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 code is shown on the right.