JOURNAL OF SHANDONG UNIVERSITY (ENGINEERING SCIENCE) ›› 2018, Vol. 48 ›› Issue (2): 134-138.doi: 10.6040/j.issn.1672-3961.0.2018.018

Previous Articles    

pH effect on the structure of Aβ42 fibrils

ZHAO Wei, AI Hongqi*   

  1. School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, Shandong, China
  • Received:2018-01-09 Online:2018-04-20 Published:2018-01-09

Abstract: To find details at atomic level for the association between structure of Aβ42 fibrils and pH, molecular dynamic simulations were preformed to study the changes in structure and property of Aβ42 fibrils at pH 4.0~7.5, by analyzing secondary structures and contents of β-sheet per chain as well as twist angles. The results showed that pH caused little change in secondary structure of fibrils. However, difference existed in content of β-sheet per chain under different pHs. The changes of twist angles and growth of fibril were initiated by the odd tip, responding to the divergence in growth mechanism of fibril.

Key words: Aβ42, pH effect, fibrils, twist angle, fibril growth, odd tip

CLC Number: 

  • O64
[1] PRINCE M, BRYCE R, ALBANESE E, et al. The global prevalence of dementia: a systematic review and metaanalysis[J]. Alzheimers & Dementia, 2013, 9(1):63-75.
[2] 陈庆华,张凤强,李立新, 等. 阿尔茨海默病发病机制和诊断技术研究进展[J]. 中华老年心脑血管病杂志, 2018, 20(1): 108-110. CHEN Qinghua, ZHANG Fengqiang, LI Lixin, et al. Advances in the pathogenesis and diagnostic techniques of Alzheimers disease[J]. Chinese Journal of Geriatric Heart Brain and Vessel Diseases, 2018, 20(1):108-110.
[3] 运会喜. 阿尔茨海默病治疗药物研究进展[J]. 中国老年学杂志, 2017, 37(24): 6269-6272. YUN Huixi. Progress in the treatment of drugs for Alzheimers Disease[J]. Chinese Journal of Gerontology, 2017, 37(24):6269-6272.
[4] CACCAMO A, ODDO S, SUGARMAN M C, et al. Age-and region-dependent alterations in Aβ-degrading enzymes: implications for Aβ-induced disorders[J]. Neurobiol of Aging, 2005, 26(5): 645-654.
[5] HARDY J, SELKOE D J. The Amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics[J]. Science, 2002, 297(5580): 353-356.
[6] MASMAN M F, EISEL U L M, CSIZMADIA I G, et al. In silico study of full-length Amyloid β1-42 tri-and penta-oligomers in solution[J]. The Journal of Physical Chemistry B, 2009, 113(34): 11710-11719.
[7] NGO S T, HUNG H M, TRUONG D T, et al. Replica exchange molecular dynamics study of the truncated amyloid beta(11-40)trimer in solution[J]. Physical Chemistry Chemical Physics, 2017, 19(3): 14876-14887.
[8] SU Y, CHANG P T. Acidic pH promotes the formation of toxic fibrils from beta-amyloid peptide[J]. Brain Research, 2001, 893(1-2): 287-291.
[9] YUN S, URBANC B, CRUZ L, et al. Role of electrostatic interactions in Amyloid β-protein(Aβ)oligomer formation: a discrete molecular dynamics study[J]. Biophysical, 2007, 92(11): 4064-4077.
[10] TIPPING K W, KARAMANOS T K, JAKHRIA T, et al. pH-induced molecular shedding drives the formation of amyloid fibril-derived oligomers[J]. Proceedings of the National Academy of Sciences, 2015, 112(18): 5691-5696.
[11] SHAMMAS S L, KNOWLES T P J, BALDWIN A J, et al. Perturbation of the stability of Amyloid fibrils through alteration of electrostatic interactions[J]. Biophysical Journal, 2011, 100(11): 2783-2791.
[12] MILLER Y, MA B, TSAI C J, et al. Hollow core of Alzheimers Aβ42 Amyloid observed by cryoEM is relevant at physiological pH[J]. Proceedings of the National Academy of Sciences, 2010, 107(32): 14128-14133.
[13] GAL BITAN M D K, ALEKSEY LOMAKIN, SABRINA S V, et al. Amyloid β-protein(Aβ)assembly: Aβ40 and Aβ42 oligomerize through distinct pathways[J]. Proceedings of the National Academy of Sciences, 2003, 100(1): 330-335.
[14] KLYUBIN I, WALSH D M, LEMERE C A, et al. Amyloid β protein immunotherapy neutralizes Aβ oligomers that disrupt synaptic plasticity in vivo[J]. Nature Medicine, 2005, 11(5): 556-561.
[15] CLEARY J P, WALSH D M, HOFMEISTER J J, et al. Natural oligomers of the Amyloid-β protein specifically disrupt cognitive function[J]. Nature Neuroscience, 2005, 8(1): 79-84.
[16] ZHAO J, WANG Q, LIANG G, et al. Molecular dynamics simulations of low-ordered Alzheimer β-Amyloid oligomers from dimer to hexamer on self-assembled monolayers[J]. Langmuir, 2011, 27(24): 14876-14887.
[17] L HRS T, RITTER C, ADRIAN M, et al. 3D structure of Alzheimers Amyloid-β(1—42)fibrils[J]. Proceedings of the National Academy of Sciences, 2005, 102(48): 17342-17347.
[18] PETTERSEN E F, GODDARD T D, HUANG C C, et al. UCSF Chimera: a visualization system for exploratory research and analysis[J]. Journal of Computational Chemistry, 2004, 25(13): 1605-1612.
[19] ANANDAKRISHNAN R, AGUILAR B, ONUFRIEV A V. H++3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations[J]. Nucleic Acids Research, 2012, 40(W1): W537-W541.
[20] DAVID V D S, LINDAHL E, HESS B, et al. GROMACS: fast, flexible, and free[J]. Journal of Computational Chemistry, 2005, 26(16): 1701-1718.
[21] HORNAK V, ABEL R, OKUR A, et al. Comparison of multiple Amber force fields and development of improved protein backbone parameters[J]. Proteins, 2006, 65(3): 712-725.
[22] DARDEN T, YORK D, PEDERSEN L. Particle mesh Ewald: an N(·overs)log(N)method for Ewald sums in large systems[J]. The Journal of Chemical Physics, 1993, 98(12): 10089-10092.
[23] UVERSKY V N, GILLESPIE J R, FINK A L. Why are "natively unfolded" proteins unstructured under physiologic conditions?[J]. Proteins, 2000, 41(3): 415-427.
[24] SCHWEIKER K L, ZARRINEAFSAR A, DAVIDSON A R, et al. Computational design of the Fyn SH3 domain with increased stability through optimization of surface charge charge interactions[J]. Protein Science, 2007, 16(12): 2694-2702.
[25] TREVINO S R, SCHAEFER S, SCHOLTZ J M, et al. Increasing protein conformational stability by optimizing β-turn sequence[J]. Journal of Molecular Biology, 2007, 373(1): 211-218.
[26] GURRY T, STULTZ C M. Mechanism of Amyloid-β fibril elongation[J]. Biochemistry Journal, 2014, 53(44): 6981-6991.
[27] PAPARCONE R, BUEHLER M J. Microscale structural model of Alzheimer Aβ(1—40)amyloid fibril[J]. Applied Physics Letters, 2009, 94(24): 243904-243904-3.
[28] HAN W, SCHULTEN K. Fibril elongation by Aβ(17-42): kinetic network analysis of hybrid-resolution molecular dynamics simulations[J]. Journal of the American Chemical Society, 2014, 136(35): 12450-12460.
[29] DONG M, PAUL T J, HOFFMANN Z, et al. Structural and material properties of Amyloid Aβ40/42 fibrils[J]. ChemPhysChem, 2016, 17(16):2558-2566.
[30] ADRIEN M, XIAO D, NORMAND M, et al. Role of the region 23-28 in Aβ fibril formation: insights from simulations of the monomers and dimers of Alzheimers peptides Aβ40 and Aβ42[J]. Current Alzheimer Research, 2008, 5(3): 244-250.
[1] SUN Limei, CUI Jie, GAO Guoqiang, LU Jianping, CEN Yuanyuan, LIU Chao, MU Xiaobin. Corrosion mechanism of metal in water injection system for Shengtuo Oilfield [J]. JOURNAL OF SHANDONG UNIVERSITY (ENGINEERING SCIENCE), 2016, 46(1): 86-92.
[2] ZHOU Mei-juan1, TIAN Chun-hua1, WANG Su-na1, CHEN Xiao-hua2, LIU Ji-feng1, ZHANG Chong1*. Theoretical study of the inclusion interaction of β-cyclodextrin with trans-Resveratrol [J]. JOURNAL OF SHANDONG UNIVERSITY (ENGINEERING SCIENCE), 2011, 41(6): 103-108.

YANG Guohui1, SUN Xiaoyu1,2*, TSUBAKI Noritatsu1

. Zeolite capsule catalyst for biogasoline [J]. JOURNAL OF SHANDONG UNIVERSITY (ENGINEERING SCIENCE), 2009, 39(2): 92-97.
[4] .

Electrode decoration and photoelectron recombination in nanocrystalline TiO2 dyesensitized solar cells

[5] WANG Lijuan, SHI Jing, ZHAO Fangjian. Molecular dynamics simulation of zwitterionic surfactant sulfobetaine at the vapor/liquid interface [J]. JOURNAL OF SHANDONG UNIVERSITY (ENGINEERING SCIENCE), 2014, 44(6): 83-89.
Full text



No Suggested Reading articles found!