Molecular metamorphosis in polcalcin allergens by EF-hand rearrangements and domain swapping

作者：Magler Iris; Nuess Dorota; Hauser Michael; Ferreira Fatima; Brandstetter Hans^*

来源：FEBS Journal, 2010, 277(12): 2598-2610.

DOI：10.1111/j.1742-4658.2010.07671.x

• covalently locked conformation
• EF-hand protein
• protein engineering
• structure
• temperature-dependent oligomerization

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.

• 出版日期2010-6