pH induced single step shift of hydrophobic patches followed by formation of an MG state and an amyloidogenic intermediate in Lima Bean Trypsin Inhibitor (LBTI)

International Journal of Biological Macromolecules
Javed M KhanSadaf Fatima

Abstract

Lima Bean Trypsin Inhibitor (LBTI) is 83 residues monomeric protein of 9.0 KDa, consisting of six antiparallel β-strands and can undergo concentration dependant dimerization. We have tried to characterize folding intermediates of LBTI under equilibrium denaturation conditions. We have used various spectroscopic and microscopic techniques to understand the folding and misfolding pathways. LBTI forms molten globule structure at pH 2 and amyloidiogenic intermediate state (I(a)) at pH 4. pH induced Shifting of surface exposed hydrophobic patches and that followed by withdrawal of the lone tyrosine residue (Y69) towards nonpolar environment have been reported. Denaturation profile of native and molten globule (MG) states of LBTI in presence of guanidine hydrochloride show sigmoidal curves with non-coincidental and irreversible behaviour in both states. Concentration dependent amyloid fibril formation was confirmed by Thioflavin T and Congo Red binding and its morphology was studied by transmission electron microscopy (TEM). This is the first report on biophysical characterization of folding intermediates of LBTI and its aggregation behaviour to the best of our knowledge.

Citations

Jun 30, 2019·International Journal of Biological Macromolecules·Roberto SantucciLaura Fiorucci

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