PDBsum entry 1h4b

Allergen

PDB id: 1h4b

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

Protein chain

Q39419  (POLC4_BETPN) -  Polcalcin Bet v 4 from Betula pendula

Seq: 85 a.a.

Struc: 84 a.a.

Enzyme reactions

• Enzyme class: E.C.?

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.