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Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics.
Journal of Mass Spectrometry ( IF 1.9 ) Pub Date : 2019-11-22 , DOI: 10.1002/jms.4470
Ahmad Kiani Karanji 1 , Maryssa Beasley 1 , Daud Sharif 1 , Ali Ranjbaran 2 , Justin Legleiter 1, 3, 4 , Stephen J Valentine 1
Affiliation  

The first 17 amino acid residues of Huntingtin protein (Nt17 of htt) are thought to play an important role in the protein's function; Nt17 is one of two membrane binding domains in htt. In this study the binding ability of Nt17 peptide with vesicles comprised of two subclasses of phospholipids is studied using electrospray ionization - mass spectrometry (ESI-MS) and molecular dynamics (MD) simulations. Overall, the peptide is shown to have a greater propensity to interact with vesicles of phosphatidylcholine (PC) rather than phosphatidylethanolamine (PE) lipids. Mass spectra show an increase in lipid-bound peptide adducts where the ordering of the number of such specie is 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) > 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) > 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphoethanolamine (POPE). MD simulations suggest that the compactness of the bilayer plays a role in governing peptide interactions. The peptide shows greater disruption of the DOPC bilayer order at the surface and interacts with the hydrophobic tails of lipid molecules via hydrophobic residues. Conversely, the POPE vesicle remains ordered and lipids display transient interactions with the peptide through the formation of hydrogen bonds with hydrophilic residues. The POPC system displays intermediate behavior with regard to the degree of peptide-membrane interaction. Finally, the simulations suggest a helix stabilizing effect resulting from the interactions between hydrophobic residues and the lipid tails of the DOPC bilayer.

中文翻译:

使用质谱和分子动力学研究Huntingtin的前17个氨基酸残基与脂质囊泡的相互作用。

亨廷顿蛋白的前17个氨基酸残基(htt的Nt17)被认为在该蛋白的功能中起着重要的作用。Nt17是htt中两个膜结合结构域之一。在这项研究中,使用电喷雾电离-质谱(ESI-MS)和分子动力学(MD)模拟研究了Nt17肽与囊泡的结合能力,囊泡包含两个亚类的磷脂。总的来说,该肽显示出比磷脂酰乙醇胺(PE)脂质更易于与磷脂酰胆碱(PC)的囊泡相互作用。质谱显示脂质结合的肽加合物增加,其中此类物质的数量顺序为1,2-二油酰基-sn-甘油-3-磷酸胆碱(DOPC)> 1-棕榈酰基-2-油酰基-甘油-3-磷酸胆碱(POPC)> 1-棕榈酰基-2-油酰基-sn-甘油-3磷酸乙醇胺(POPE)。MD模拟表明,双层的紧密性在控制肽相互作用中起作用。该肽在表面上显示出更大的DOPC双层顺序破坏,并通过疏水残基与脂质分子的疏水尾相互作用。相反,POPE囊泡保持有序,脂质通过与亲水性残基形成氢键而显示出与肽的短暂相互作用。POPC系统显示有关肽膜相互作用程度的中间行为。最后,模拟结果表明,疏水性残基和DOPC双层脂质尾部之间的相互作用产生了螺旋稳定作用。该肽在表面上显示出更大的DOPC双层顺序破坏,并通过疏水残基与脂质分子的疏水尾相互作用。相反,POPE囊泡保持有序,脂质通过与亲水性残基形成氢键而显示出与肽的短暂相互作用。POPC系统显示有关肽膜相互作用程度的中间行为。最后,模拟结果表明,疏水性残基和DOPC双层脂质尾部之间的相互作用产生了螺旋稳定作用。该肽在表面上显示出更大的DOPC双层顺序破坏,并通过疏水残基与脂质分子的疏水尾相互作用。相反,POPE囊泡保持有序,脂质通过与亲水性残基形成氢键而显示出与肽的短暂相互作用。POPC系统显示有关肽膜相互作用程度的中间行为。最后,模拟结果表明,疏水性残基和DOPC双层脂质尾部之间的相互作用产生了螺旋稳定作用。POPE囊泡保持有序,脂质通过与亲水性残基形成氢键而显示出与肽的短暂相互作用。POPC系统显示有关肽膜相互作用程度的中间行为。最后,模拟结果表明,疏水性残基和DOPC双层脂质尾部之间的相互作用产生了螺旋稳定作用。POPE囊泡保持有序,脂质通过与亲水性残基形成氢键,表现出与肽的短暂相互作用。POPC系统显示有关肽膜相互作用程度的中间行为。最后,模拟结果表明,疏水性残基和DOPC双层脂质尾部之间的相互作用产生了螺旋稳定作用。
更新日期:2020-01-14
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