胰岛淀粉样多肽的环状 N 端环形成非淀粉样纤维。
Cyclic N-terminal loop of amylin forms non amyloid fibers.
机构信息
Center for Biological Physics, Arizona State University, Tempe, Arizona; Department of Physics, Arizona State University, Tempe, Arizona.
出版信息
Biophys J. 2013 Oct 1;105(7):1661-9. doi: 10.1016/j.bpj.2013.08.026.
Abstract
We report for the first time, to our knowledge, that the N-terminal loop (N_loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) forms extremely long and stable non-β-sheet fibers in solution under the same conditions in which human amylin (hIAPP) forms amyloid fibers. This observation applies to the cyclic, oxidized form of the N_loop but not to the linear, reduced form, which does not form fibers. Our findings indicate a potential role of direct N_loop-N_loop interactions in hIAPP aggregation, which has not been previously explored, with important implications for the mechanism of hIAPP amyloid fiber formation, the inhibitory action of IAPP variants, and the competition between ordered and disordered aggregation in peptides of the calcitonin peptide family.
摘要
我们首次报告，据我们所知，在相同条件下，胰岛淀粉样多肽（IAPP）残基 1-8 的 N 端环（N 环）在溶液中形成极其长且稳定的非 β-折叠纤维，而人胰岛淀粉样多肽（hIAPP）则形成淀粉样纤维。这一观察结果适用于 N 环的环状、氧化形式，但不适用于线性、还原形式，因为线性、还原形式不会形成纤维。我们的发现表明，N 环-N 环相互作用可能在 hIAPP 聚集中发挥作用，这一作用以前尚未被探索过，对 hIAPP 淀粉样纤维形成机制、IAPP 变体的抑制作用以及降钙素肽家族中有序和无序聚集之间的竞争具有重要意义。
相似文献
1
Cyclic N-terminal loop of amylin forms non amyloid fibers.胰岛淀粉样多肽的环状 N 端环形成非淀粉样纤维。
Biophys J. 2013 Oct 1;105(7):1661-9. doi: 10.1016/j.bpj.2013.08.026.
2
Structural and energetic insight into the cross-seeding amyloid assemblies of human IAPP and rat IAPP.对人胰岛淀粉样多肽（IAPP）和大鼠IAPP交叉播种淀粉样聚集体的结构与能量洞察。
J Phys Chem B. 2014 Jun 26;118(25):7026-36. doi: 10.1021/jp5022246. Epub 2014 Jun 12.
3
Comparative molecular dynamics study of human islet amyloid polypeptide (IAPP) and rat IAPP oligomers.人胰岛淀粉样多肽（IAPP）和大鼠 IAPP 寡聚物的比较分子动力学研究。
Biochemistry. 2013 Feb 12;52(6):1089-100. doi: 10.1021/bi301525e. Epub 2013 Jan 29.
4
Membrane disruption and early events in the aggregation of the diabetes related peptide IAPP from a molecular perspective.从分子角度看糖尿病相关肽 IAPP 的聚集过程中膜的破坏和早期事件。
Acc Chem Res. 2012 Mar 20;45(3):454-62. doi: 10.1021/ar200189b. Epub 2011 Sep 25.
5
Structure and thermodynamics of amylin dimer studied by Hamiltonian-temperature replica exchange molecular dynamics simulations.通过哈密顿温度复制交换分子动力学模拟研究淀粉样肽二聚体的结构和热力学性质。
J Phys Chem B. 2011 Mar 31;115(12):3146-54. doi: 10.1021/jp108870q. Epub 2011 Mar 8.
6
Analysis of the ability of pramlintide to inhibit amyloid formation by human islet amyloid polypeptide reveals a balance between optimal recognition and reduced amyloidogenicity.普兰林肽抑制人胰岛淀粉样多肽形成淀粉样蛋白能力的分析揭示了最佳识别与降低淀粉样蛋白生成性之间的平衡。
Biochemistry. 2015 Nov 10;54(44):6704-11. doi: 10.1021/acs.biochem.5b00567. Epub 2015 Oct 30.
7
Comparing the structural properties of human and rat islet amyloid polypeptide by MD computer simulations.通过 MD 计算机模拟比较人胰岛淀粉样多肽和大鼠胰岛淀粉样多肽的结构特性。
Biophys Chem. 2011 Jun;156(1):43-50. doi: 10.1016/j.bpc.2010.12.007. Epub 2010 Dec 31.
8
All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints.通过增强采样和实验数据约束确定的胰岛淀粉样多肽的全原子结构集合。
Proteins. 2019 Jul;87(7):541-550. doi: 10.1002/prot.25677. Epub 2019 Mar 6.
9
The pressure and temperature perturbation approach reveals a whole variety of conformational substates of amyloidogenic hIAPP monitored by 2D NMR spectroscopy.压力和温度微扰方法揭示了通过 2D NMR 光谱监测到的淀粉样蛋白原性 hIAPP 的各种构象亚稳态。
Biophys Chem. 2019 Nov;254:106239. doi: 10.1016/j.bpc.2019.106239. Epub 2019 Jul 30.
10
Structural polymorphism of human islet amyloid polypeptide (hIAPP) oligomers highlights the importance of interfacial residue interactions.人胰岛淀粉样多肽（hIAPP）寡聚物的结构多态性突出了界面残基相互作用的重要性。
Biomacromolecules. 2011 Jan 10;12(1):210-20. doi: 10.1021/bm101159p. Epub 2010 Dec 15.
引用本文的文献
1
Structural Characterization of Fibrils from Recombinant Human Islet Amyloid Polypeptide by Solid-State NMR: The Central FGAILS Segment Is Part of the β-Sheet Core.通过固态核磁共振对重组人胰岛淀粉样多肽原纤维的结构表征：中央FGAILS片段是β-折叠核心的一部分。
PLoS One. 2016 Sep 8;11(9):e0161243. doi: 10.1371/journal.pone.0161243. eCollection 2016.
2
Human Islet Amyloid Polypeptide N-Terminus Fragment Self-Assembly: Effect of Conserved Disulfide Bond on Aggregation Propensity.人胰岛淀粉样多肽 N 端片段自组装：保守二硫键对聚集倾向的影响。
J Am Soc Mass Spectrom. 2016 Jun;27(6):1010-8. doi: 10.1007/s13361-016-1347-7. Epub 2016 Feb 19.
3
Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP: A Comparison with Amylin.无序蛋白降钙素基因相关肽的慢内禀动力学和电荷扩展：与胰淀素的比较。
Biophys J. 2015 Sep 1;109(5):1038-48. doi: 10.1016/j.bpj.2015.07.023.
本文引用的文献
1
Two-dimensional infrared spectroscopy reveals the complex behaviour of an amyloid fibril inhibitor.二维红外光谱揭示了淀粉样纤维抑制剂的复杂行为。
Nat Chem. 2012 Mar 11;4(5):355-60. doi: 10.1038/nchem.1293.
2
Disordered proteins studied by chemical shifts.通过化学位移研究的无序蛋白质。
Prog Nucl Magn Reson Spectrosc. 2012 Jan;60:42-51. doi: 10.1016/j.pnmrs.2011.10.001. Epub 2011 Oct 12.
3
Islet amyloid polypeptide, islet amyloid, and diabetes mellitus.胰岛淀粉样多肽、胰岛淀粉样变和糖尿病。
Physiol Rev. 2011 Jul;91(3):795-826. doi: 10.1152/physrev.00042.2009.
4
A diversity of assembly mechanisms of a generic amyloid fold.多种通用淀粉样纤维折叠的组装机制。
Mol Cell. 2011 Jul 8;43(1):8-18. doi: 10.1016/j.molcel.2011.05.012.
5
Sequence correction of random coil chemical shifts: correlation between neighbor correction factors and changes in the Ramachandran distribution.随机卷曲化学位移的序列校正：相邻校正因子的变化与 Ramachandran 分布的变化之间的相关性。
J Biomol NMR. 2011 Jun;50(2):157-65. doi: 10.1007/s10858-011-9508-2. Epub 2011 May 22.
6
The amyloid formation mechanism in human IAPP: dimers have β-strand monomer-monomer interfaces.人胰岛素样肽的淀粉样形成机制：二聚体具有β-折叠单体-单体界面。
J Am Chem Soc. 2011 May 18;133(19):7240-3. doi: 10.1021/ja1081537. Epub 2011 Apr 25.
7
Sequence-specific random coil chemical shifts of intrinsically disordered proteins.无规卷曲蛋白质的序列特异性随机卷曲化学位移。
J Am Chem Soc. 2010 Dec 29;132(51):18000-3. doi: 10.1021/ja105656t. Epub 2010 Dec 3.
8
Combination of kinetically selected inhibitors in trans leads to highly effective inhibition of amyloid formation.动力学选择抑制剂的组合在反义链上导致淀粉样形成的高效抑制。
J Am Chem Soc. 2010 Oct 20;132(41):14340-2. doi: 10.1021/ja1046186.
9
Residue-specific, real-time characterization of lag-phase species and fibril growth during amyloid formation: a combined fluorescence and IR study of p-cyanophenylalanine analogs of islet amyloid polypeptide.残基特异性、实时鉴定淀粉样形成过程中的滞后相物种和原纤维生长：对胰岛淀粉样多肽的 p-氰基苯丙氨酸类似物进行的荧光和红外联合研究。
J Mol Biol. 2010 Jul 23;400(4):878-88. doi: 10.1016/j.jmb.2010.05.041. Epub 2010 Jun 1.
10
SPARTA+: a modest improvement in empirical NMR chemical shift prediction by means of an artificial neural network.SPARTA+：通过人工神经网络对经验核磁共振化学位移预测的适度改进。
J Biomol NMR. 2010 Sep;48(1):13-22. doi: 10.1007/s10858-010-9433-9. Epub 2010 Jul 14.
Zotero 插件