PH-Induced Local Unfolding of the Phl p 6 Pollen Allergen From cpH-MD.

ABSTRACT: Susceptibility to endosomal degradation is a decisive contribution to a protein's immunogenicity. It is assumed that the processing kinetics of structured proteins are inherently linked to their probability of local unfolding. In this study, we quantify the impact of endosomal acidification on the conformational stability of the major timothy grass pollen allergen Phl p 6. We use state of the art sampling approaches in combination with constant pH MD techniques to profile pH-dependent local unfolding events in atomistic detail. Integrating our findings into the current view on type 1 allergic sensitization, we characterize local protein dynamics in the context of proteolytic degradation at neutral and acidic pH for the wild type protein and point mutants with varying proteolytic stability.

SUBMITTER: Hofer F 

PROVIDER: S-EPMC7835895 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature