title: Effects of His mutations on the fibrillation of amyloidogenic Vlambda6 protein Wil under acidic and physiological conditions.
abstract: Recently, we showed that the recombinant (r) Vlambda6 protein Wil exhibits a more disrupted residual structure and a longer lag time for fibril formation than the rVlambda6 protein Jto under highly unfolding conditions at pH 2. Here, we focused on the roles of three histidine residues specific for Wil, which are positively charged at pH 2 and could repel one another. Heteronuclear relaxation experiments revealed that a mutant Wil with H34Q, H53Q and H93S mutations (3HmutWil) had larger R(2) values only in the region of residues 22-55 and formed fibrils much earlier than Wil at pH 2. 3HmutWil also showed a decrease in ThT fluorescence intensity compared with Wil in fibrillation experiments at pH 7.5. The present results suggest that these three histidine residues play important roles in the fibrillation of Wil at both pH 2 and pH 7.5.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Mishima
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Ohkuri
authors.forename: Akira
authors.initials: A
authors.lastname: Monji
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kanemaru
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Abe
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053616:Janus Kinase 3 / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D011994:Recombinant Proteins; D006639:Histidine; C507933:JAK3 protein, human; D053616:Janus Kinase 3