Conformational Flexibility Differentiates Naturally Occurring Bet v 1 Isoforms
AbstractThe protein Bet v 1 represents the main cause for allergic reactions to birch pollen in Europe and North America. Structurally homologous isoforms of Bet v 1 can have different properties regarding allergic sensitization and Th2 polarization, most likely due to differential susceptibility to proteolytic cleavage. Using NMR relaxation experiments and molecular dynamics simulations, we demonstrate that the initial proteolytic cleavage sites in two naturally occurring Bet v 1 isoforms, Bet v 1.0101 (Bet v 1a) and Bet v 1.0102 (Bet v 1d), are conformationally flexible. Inaccessible cleavage sites in helices and strands are highly flexible on the microsecond-millisecond time scale, whereas those located in loops display faster nanosecond-microsecond flexibility. The data consistently show that Bet v 1.0102 is more flexible and conformationally heterogeneous than Bet v 1.0101. Moreover, NMR hydrogen-deuterium exchange measurements reveal that the backbone amides in Bet v 1.0102 are significantly more solvent exposed, in agreement with this isoform’s higher susceptibility to proteolytic cleavage. The differential conformational flexibility of Bet v 1 isoforms, along with the transient exposure of inaccessible sites to the protein surface, may be linked to proteolytic susceptibility, representing a potential structure-based rationale for the observed differences in Th2 polarization and allergic sensitization. View Full-Text
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Grutsch, S.; Fuchs, J.E.; Ahammer, L.; Kamenik, A.S.; Liedl, K.R.; Tollinger, M. Conformational Flexibility Differentiates Naturally Occurring Bet v 1 Isoforms. Int. J. Mol. Sci. 2017, 18, 1192.
Grutsch S, Fuchs JE, Ahammer L, Kamenik AS, Liedl KR, Tollinger M. Conformational Flexibility Differentiates Naturally Occurring Bet v 1 Isoforms. International Journal of Molecular Sciences. 2017; 18(6):1192.Chicago/Turabian Style
Grutsch, Sarina; Fuchs, Julian E.; Ahammer, Linda; Kamenik, Anna S.; Liedl, Klaus R.; Tollinger, Martin. 2017. "Conformational Flexibility Differentiates Naturally Occurring Bet v 1 Isoforms." Int. J. Mol. Sci. 18, no. 6: 1192.
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