Steric Zipper Formed by Hydrophobic Peptide Fragment of Syrian Hamster Prion Protein
Steric Zipper Formed by Hydrophobic Peptide Fragment of Syrian Hamster Prion Protein
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DOI：
10.1021/bi200712z
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发表时间：
2011-08-16
期刊：
影响因子：
2.9
通讯作者：
Chan, Jerry C. C.
中科院分区：
文献类型：
--
作者：
Cheng, Hsin-Mei;Tsai, Tim W. T.;Chan, Jerry C. C.
Eisenberg和他的同事提出，两个相邻的β -片层的残基紧密交错的立体拉链是淀粉样原纤维的基本结构单位。由含有回文序列AGAAAAGA的多肽组成的立体拉链具有显著的特征，即两个互指的β -片层之间的距离与单个β -片的链间距离相当。由于AGAAAAGA序列在不同物种的朊病毒蛋白中高度保守，该结构基序在朊病毒疾病的研究中具有重要意义。本研究以PrP（113-127）多肽形成的淀粉样原纤维Ac-AGAAAAGAVVGGLGG-NH(2)为模型化合物，研究控制立体拉链形成的生物物理原理。靶原纤维采用7级立体拉链的结构基序，该结构基序由反平行的β片层堆叠而成，残基117 + k与残基120 - k形成主氢键。
Steric zippers, where the residues of two neighboring beta-sheet layers are tightly interdigitated, have been proposed as fundamental structural units of amyloid fibrils by Eisenberg and co-workers. The steric zipper formed by polypeptides containing the palindromic sequence AGAAAAGA has a distinctive feature that the distance between two interdigitated beta-sheet layers is comparable to the interstrand distance of the individual beta-sheet. This structural motif is of great interest in the study of prion disease because the AGAAAAGA sequence is highly conserved in prion proteins of different species. In this work, the amyloid fibrils formed by the polypeptides of PrP(113-127), viz. Ac-AGAAAAGAVVGGLGG-NH(2), are taken as the model compound to investigate the biophysical principles governing the steric zipper formation. The target fibrils adopt the structural motif of class 7 steric zipper, which is formed by stacking of antiparallel beta-sheet layers with residue 117 + k forming backbone hydrogen bonds to residue 120 - k. Implication of our results in the infectivity of scrapie prion is briefly discussed.