Molecular metamorphosis in polcalcin allergens by EF-hand rearrangements and domain swapping.
Polcalcins such as Bet v 4 and Phl p 7 are pollen allergens that are constructed from EF-hand motifs, which are very common and well characterized helix-loop-helix motifs with calcium-binding functions, as elementary building blocks. Being members of an exceptionally well-characterized protein superfamily, these allergens highlight the fundamental challenge in explaining what features distinguish allergens from nonallergenic proteins. We found that Bet v 4 and Phl p 7 undergo oligomerization transitions with characteristics that are markedly different from those typically found in proteins: transitions from monomers to dimers and to distinct higher oligomers can be induced by increasing temperature; similarly, low concentrations of destabilizing agents, e.g. SDS, induce oligomerization transitions of Bet v 4. The changes in the quaternary structure, termed molecular metamorphosis, are induced and controlled by a combination of EF-hand rearrangements and domain swapping rather than by the classical law of mass action. Using an EF-hand-pairing model, we provide a two-step model that consistently explains and substantiates the observed metamorphosis. Moreover, the unusual oligomerization behavior suggests a straightforward explanation of how allergens can accomplish the crosslinking of IgE on mast cells, a hallmark of allergens.
Magler
Iris
I
Division of Structural Biology, Department of Molecular Biology, University of Salzburg, Austria.
Nüss
Dorota
D
Hauser
Michael
M
Ferreira
Fatima
F
Brandstetter
Hans
H
D000485:Allergens / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D052179:Antigens, Plant; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D002850:Chromatography, Gel; D020832:EF Hand Motifs / Q000276:immunology; D004926:Escherichia coli / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D011487:Protein Conformation / Q000187:drug effects; D055503:Protein Multimerization; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013696:Temperature; D013816:Thermodynamics
D000485:Allergens; D052179:Antigens, Plant; C108867:BETV4 protein, Betula pendula; D002135:Calcium-Binding Proteins; C468525:Phl p 7 allergen; D010940:Plant Proteins; D012967:Sodium Dodecyl Sulfate