TAILIEUCHUNG - Báo cáo khoa học: 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 con-structed from EF-hand motifs, which are very common and well character-ized 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. | Molecular metamorphosis in polcalcin allergens by EF-hand rearrangements and domain swapping Iris Magler1 Dorota Nuss1 Michael Hauser2 Fatima Ferreira2 and Hans Brandstetter1 1 Division of StructuralBiology Department of Molecular Biology University of Salzburg Austria 2 Division of Allergy Department of Molecular Biology University of Salzburg Austria Keywords covalently locked conformation EF-hand protein protein engineering structure temperature-dependent oligomerization Correspondence H. Brandstetter Billrothstr. 11 5020 Salzburg Austria Fax 43 662 8044 7209 Tel 43 662 8044 7270 E-mail Received 5 February 2010 revised 17 March 2010 accepted 7 April 2010 doi 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 . 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 .

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