Authors: Noriko Fujii Norihiko Fujii Masashi Kida Tadatoshi Kinouchi
Publish Date: 2010/05/01
Volume: 39, Issue: 5, Pages: 1393-1399
Abstract
Proteins have been considered to consist exclusively of lamino acids in living tissues However our previous studies showed that two specific aspartyl Asp residues in αA and αBcrystallins from human eye lenses invert to the disomers to a high degree during aging The reaction is also accompanied by isomerization into a form containing βAsp isoaspartate residues The appearance of d and βAsp in a protein potentially induces large changes to the higher order structure of the protein as well as to its function However it remains unclear whether the formation of the Asp isomer is the direct trigger of the change to the higher order structure and function In this study in order to clarify the effect of the inversion to disomers in a protein we synthesized peptides corresponding to the 70–88 KFVIFLDVKHFSPEDLTVK fragment of human αAcrystallin and its corresponding diastereoisomers in which lαAsp was replaced with lβAsp dαAsp and dβAsp at position 76 and compared their biochemical properties with that of normal peptide The peptides containing abnormal isomers lβAsp dαAsp and dβAsp residues respectively were more hydrophilic than the normal peptide containing lαAsp lost βsheet structure and changed to random structures The normal peptide promoted the aggregation of insulin while the other three isomers suppressed the aggregation of insulin This is the first evidence that a single substitution of an Asp isomer in a peptide induces a large change to the properties of the peptide
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