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環狀序列重組應用在具有CSαβ模組的綠豆防禦素第一型之研究
Thesis

環狀序列重組應用在具有CSαβ模組的綠豆防禦素第一型之研究

許宏嘉
Masters, 國立清華大學, 生物資訊與結構生物研究所
2014

Abstract

環狀序列重組 綠豆植物防禦素第一型 VrD1 Circular permutation cysteine- stabilized αβ motif
Mung bean (Vigna radiata) plant defensin 1 (VrD1) is the first reported plant defensin, which exhibits insecticidal activity against Callosobruchus chinensis (bruchid). VrD1 is a 46-residue basic peptide containing a cysteine-stabilized αβ (CSαβ) motif with four disulfide-bonds to stable its structure. Three dimensional structure determined by nuclear magnetic resonance (NMR) spectroscopy and alanine substitutions of noncysteine residues in VrD1 were done in our lab. Our previous studies showed that the loop L3 and the 310 helix played important roles in VrD1 insecticidal function. In this study, a protein engineering method – circular permutation (CP) – was employed on VrD1. The CP rearrangement in a protein is visualized as that the original termini of polypeptide are linked and new termini are created elsewhere. The CP rearranged proteins can be utilized to explore protein folding, stability of structure, and functions. Two CP-VrD1 proteins with residue M36 as the new N-terminus and linkers of one and two glycine (VrD1 CP36_G and VrD1 CP36_2G, respectively) were obtained and investigated. VrD1 CP36_G lost almost all structure and function, while VrD1 CP36_2G kept both characters. The length of linker for native termini may affect the protein folding, and our results revealed that the length of linker should be longer than the distance between the native N- and C-termini. VrD1 CP36_2G inhibited α-amylase although the new termini were created at the functional loop L3 and its IC50 was 1.93 μM while that of wild type VrD1 was 3.14 μM. So the important role of loop L3 may be to display the positively charged residues which participated in the electrostatic interaction between VrD1 and TMA.

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