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Acidic pH retards the fibrillization of human islet amyloid polypeptide due to electrostatic repulsion of histidines

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Acidic pH retards the fibrillization of human islet amyloid polypeptide due to electrostatic repulsion of histidines
นักวิจัย : Li, Yang , Xu, Weixin , Mu, Yuguang , Zhang, John Z. H.
คำค้น : DRNTU::Science::Biological sciences.
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2556
อ้างอิง : Li, Y., Xu, W., Mu, Y., & Zhang, J. Z. H. (2013). Acidic pH retards the fibrillization of human islet amyloid polypeptide due to electrostatic repulsion of histidines. The Journal of Chemical Physics, 139(5), 055102. , 0021-9606 , http://hdl.handle.net/10220/13354 , http://dx.doi.org/10.1063/1.4817000
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : The journal of chemical physics
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

The human Islet Amyloid Polypeptide (hIAPP) is the major constituent of amyloid deposits in pancreatic islets of type-II diabetes. IAPP is secreted together with insulin from the acidic secretory granules at a low pH of approximately 5.5 to the extracellular environment at a neutral pH. The increased accumulation of extracellular hIAPP in diabetes indicates that changes in pH may promote amyloid formation. To gain insights and underlying mechanisms of the pH effect on hIAPP fibrillogenesis, all-atom molecular dynamics simulations in explicit solvent model were performed to study the structural properties of five hIAPP protofibrillar oligomers, under acidic and neutral pH, respectively. In consistent with experimental findings, simulation results show that acidic pH is not conducive to the structural stability of these oligomers. This provides a direct evidence for a recent experiment [L. Khemtemourian, E. Domenech, J. P. F. Doux, M. C. Koorengevel, and J. A. Killian, J. Am. Chem. Soc. 133, 15598 (2011)]10.1021/ja205007j, which suggests that acidic pH inhibits the fibril formation of hIAPP. In addition, a complementary coarse-grained simulation shows the repulsive electrostatic interactions among charged His18 residues slow down the dimerization process of hIAPP by twofold. Besides, our all-atom simulations reveal acidic pH mainly affects the local structure around residue His18 by destroying the surrounding hydrogen-bonding network, due to the repulsive interactions between protonated interchain His18 residues at acidic pH. It is also disclosed that the local interactions nearby His18 operating between adjacent β-strands trigger the structural transition, which gives hints to the experimental findings that the rate of hIAPP fibril formation and the morphologies of the fibrillar structures are strongly pH-dependent

บรรณานุกรม :
Li, Yang , Xu, Weixin , Mu, Yuguang , Zhang, John Z. H. . (2556). Acidic pH retards the fibrillization of human islet amyloid polypeptide due to electrostatic repulsion of histidines.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Li, Yang , Xu, Weixin , Mu, Yuguang , Zhang, John Z. H. . 2556. "Acidic pH retards the fibrillization of human islet amyloid polypeptide due to electrostatic repulsion of histidines".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Li, Yang , Xu, Weixin , Mu, Yuguang , Zhang, John Z. H. . "Acidic pH retards the fibrillization of human islet amyloid polypeptide due to electrostatic repulsion of histidines."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2556. Print.
Li, Yang , Xu, Weixin , Mu, Yuguang , Zhang, John Z. H. . Acidic pH retards the fibrillization of human islet amyloid polypeptide due to electrostatic repulsion of histidines. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2556.