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PDBsum entry 1h4b

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protein metals links
Allergen PDB id
1h4b
Jmol
Contents
Protein chain
84 a.a. *
Metals
_CA ×2
* Residue conservation analysis
PDB id:
1h4b
Name: Allergen
Title: Solution structure of the birch pollen allergen bet v 4
Structure: Polcalcin bet v 4. Chain: a. Synonym: calcium-binding pollen allergen bet v 4. Engineered: yes
Source: Betula verrucosa. White birch. Organism_taxid: 3505. Expressed in: escherichia coli. Expression_system_taxid: 469008.
NMR struc: 25 models
Authors: P.Neudecker,J.Nerkamp,A.Eisenmann,T.Lauber,K.Lehmann, K.Schweimer,P.Roesch
Key ref:
P.Neudecker et al. (2004). Solution structure, dynamics, and hydrodynamics of the calcium-bound cross-reactive birch pollen allergen Bet v 4 reveal a canonical monomeric two EF-hand assembly with a regulatory function. J Mol Biol, 336, 1141-1157. PubMed id: 15037075 DOI: 10.1016/j.jmb.2003.12.070
Date:
26-Feb-03     Release date:   26-Feb-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q39419  (POLC4_BETPN) -  Polcalcin Bet v 4
Seq:
Struc:
85 a.a.
84 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     metal ion binding     2 terms  

 

 
DOI no: 10.1016/j.jmb.2003.12.070 J Mol Biol 336:1141-1157 (2004)
PubMed id: 15037075  
 
 
Solution structure, dynamics, and hydrodynamics of the calcium-bound cross-reactive birch pollen allergen Bet v 4 reveal a canonical monomeric two EF-hand assembly with a regulatory function.
P.Neudecker, J.Nerkamp, A.Eisenmann, A.Nourse, T.Lauber, K.Schweimer, K.Lehmann, S.Schwarzinger, F.Ferreira, P.Rösch.
 
  ABSTRACT  
 
Birch pollinosis is one of the prevailing allergic diseases. In all, 5-20% of birch pollinotics mount IgE antibodies against the minor birch pollen allergen Bet v 4, a Ca2+-binding polcalcin. Due to IgE cross-reactivity among the polcalcins these patients are polysensitized to various plant pollens. Determination of the high-resolution structure of holo Bet v 4 by heteronuclear NMR spectroscopy reveals a canonical two EF-hand assembly in the open conformation with interhelical angles closely resembling holo calmodulin. The polcalcin-specific amphipathic COOH-terminal alpha-helix covers only a part of the hydrophobic groove on the molecular surface. Unlike the polcalcin Phl p 7 from timothy grass, which was recently shown to form a domain-swapped dimer, the hydrodynamic parameters from NMR relaxation, NMR translational diffusion, and analytical ultracentrifugation indicate that both apo and holo Bet v 4 are predominantly monomeric, raising the question of the physiological and immunological significance of the dimeric form of these polcalcins, whose physiological function is still unknown. The reduced helicity and heat stability in the CD spectra, the poor chemical shift dispersion of the NMR spectra, and the slightly increased hydrodynamic radius of apo Bet v 4 indicate a reversible structural transition upon Ca2+ binding, which explains the reduced IgE binding capacity of apo Bet v 4. The remarkable structural similarity of holo Bet v 4 and holo Phl p 7 in spite of different oligomerization states explains the IgE cross-reactivity and indicates that canonical monomers and domain-swapped dimers may be of similar allergenicity. Together with the close structural homology to calmodulin and the hydrophobic ligand binding groove this transition suggests a regulatory function for Bet v 4.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Connolly surface of the lowest energy structure of holo Bet v 4 colored according to hydrophobicity (top; backbone yellow, hydrophobic residues green, hydrophilic residues blue) or electrostatic potential (bottom; negative potential red, positive potential blue). Opposite view as in Figure 4 and Figure 5. The electric charge of the side-chain of His48 depends on pH, at pH 6.0 it is predominantly protonated. The COOH-terminal helix a[5] does not cover the hydrophobic groove lined by negatively charged residues completely. Formation of the domain-swapped dimer of holo Phl p 7 closes this hydrophobic groove, resulting in a hydrophobic cavity which is no longer solvent-accessible.[26.] The Figure was prepared with InsightII 98.0 (Molecular Simulations Inc., San Diego, CA, USA) and GRASP 1.2. [94.]
Figure 8.
Figure 8. Backbone overlay of the average solution structure of holo Bet v 4 (yellow) with the NH[2]-terminal EF-hand of the first monomer (green) and the COOH-terminal EF-hand of the second monomer (blue) of the crystal structure of holo Phl p 7. Apart from the domain-swapping dimerization the tertiary fold is almost identical. The overlay was performed using Sybyl 6.5 (Tripos Inc., St. Louis, MO, USA).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 336, 1141-1157) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20553495 I.Magler, D.Nüss, M.Hauser, F.Ferreira, and H.Brandstetter (2010).
Molecular metamorphosis in polcalcin allergens by EF-hand rearrangements and domain swapping.
  FEBS J, 277, 2598-2610.  
18683824 G.Marzban, A.Herndl, D.Kolarich, F.Maghuly, A.Mansfeld, W.Hemmer, H.Katinger, and M.Laimer (2008).
Identification of four IgE-reactive proteins in raspberry (Rubus ideaeus L.).
  Mol Nutr Food Res, 52, 1497-1506.  
18184590 M.T.Naik, C.F.Chang, I.C.Kuo, C.C.Kung, F.C.Yi, K.Y.Chua, and T.H.Huang (2008).
Roles of structure and structural dynamics in the antibody recognition of the allergen proteins: an NMR study on Blomia tropicalis major allergen.
  Structure, 16, 125-136.
PDB code: 2jmh
16512810 A.Ledesma, R.Barderas, K.Westritschnig, J.Quiralte, C.Y.Pascual, R.Valenta, M.Villalba, and R.Rodríguez (2006).
A comparative analysis of the cross-reactivity in the polcalcin family including Syr v 3, a new member from lilac pollen.
  Allergy, 61, 477-484.  
15987884 A.Eisenmann, S.Schwarz, S.Prasch, K.Schweimer, and P.Rösch (2005).
The E. coli NusA carboxy-terminal domains are structurally similar and show specific RNAP- and lambdaN interaction.
  Protein Sci, 14, 2018-2029.
PDB codes: 1wcl 1wcn
15937283 D.V.Venkitaramani, D.B.Fulton, A.H.Andreotti, K.M.Johansen, and J.Johansen (2005).
Solution structure and backbone dynamics of Calsensin, an invertebrate neuronal calcium-binding protein.
  Protein Sci, 14, 1894-1901.
PDB codes: 1yx7 1yx8
16264339 R.W.Weber (2005).
Cross-reactivity of pollen allergens: recommendations for immunotherapy vaccines.
  Curr Opin Allergy Clin Immunol, 5, 563-569.  
15283881 R.W.Weber (2004).
Cross-reactivity of pollen allergens.
  Curr Allergy Asthma Rep, 4, 401-408.  
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.