Elongation kinetics of polyglutamine peptide fibrils: a quartz crystal microbalance with dissipation study.
Elongation kinetics of polyglutamine peptide fibrils: a quartz crystal microbalance with dissipation study.
复制标题
DOI：
10.1016/j.jmb.2012.03.017
复制
发表时间：
2012-08-10
影响因子：
5.6
通讯作者：
Murphy, Regina M.
中科院分区：
文献类型：
--
作者：
Walters, Robert H.;Jacobson, Kurt H.;Pedersen, Joel A.;Murphy, Regina M.
关键词：
蛋白质中异常扩增的多聚谷氨酰胺结构域与包括亨廷顿病在内的几种神经退行性疾病有关。多聚谷氨酰胺（polyQ）结构域的扩展促进了受影响蛋白质的聚集，一些研究直接将聚集与神经毒性联系起来。合成polyQ肽的研究大大有助于我们理解的聚集机制。在这份报告中，polyQ原纤维被固定到传感器上，并使用石英晶体微天平与耗散监测（QCM-D）的polyQ肽的各种长度和构象的延长进行了检查。随着肽长度从8个谷氨酰胺增加到24个谷氨酰胺（Q8、Q20和Q24），延伸速率增加。膜构象影响延伸速率：在肽中心插入β-转角模板d-Pro-Gly使延伸速率增加数倍，而插入Pro-Pro显著减慢延伸。QCM-D的耗散测量提供了关于伸长原纤维的机械性能的定性信息。这些数据显示了延伸聚集体的特征的明显差异，这取决于缔合polyQ肽的特定身份。延伸率对缓冲液的pH和离子强度敏感。比较QCM-D数据与光波导光模光谱法得到的结果表明，很少的水与含有d-Pro-Gly的肽的原纤维的伸长相关，但当原纤维被Q20伸长时，有大量的水相关。总之，数据表明，polyQ原纤维的伸长可以在没有完全固结成原纤维结构的情况下发生，从而导致在伸长期间聚集体结构的变化。
Abnormally expanded polyglutamine domains in proteins are associated with several neurodegenerative diseases, including Huntington's disease. Expansion of the polyglutamine (polyQ) domain facilitates aggregation of the affected protein, and several studies directly link aggregation to neurotoxicity. Studies of synthetic polyQ peptides have contributed substantially to our understanding of the mechanism of aggregation. In this report, polyQ fibrils were immobilized onto a sensor, and their elongation by polyQ peptides of various length and conformation was examined using quartz crystal microbalance with dissipation monitoring (QCM-D). The rate of elongation increased as the peptide length increased from 8 to 24 glutamines (Q8, Q20, and Q24). Monomer conformation affected elongation rates: insertion of a β-turn template d-Pro-Gly in the center of the peptide increased elongation rates several-fold, while insertion of Pro-Pro dramatically slowed elongation. Dissipation measurements of the QCM-D provided qualitative information about mechanical properties of the elongating fibrils. These data showed clear differences in the characteristics of the elongating aggregates, depending on the specific identity of the associating polyQ peptide. Elongation rates were sensitive to the pH and ionic strength of the buffer. Comparison of QCM-D data with those obtained by optical waveguide lightmode spectroscopy revealed that very little water was associated with the elongation of fibrils by the peptide containing d-Pro-Gly, but a significant amount of water was associated when the fibrils were elongated by Q20. Together, the data indicate that elongation of polyQ fibrils can occur without full consolidation to the fibril structure, resulting in variations to the aggregate structure during elongation.
登录
查看更多内容
影响因子：
3.4
作者：
Hovgaard, Mads Bruun;Dong, Mingdong;Besenbacher, Flemming
通讯作者：
Besenbacher, Flemming
DOI：
10.1073/pnas.0911107107
发表时间：
2010-05-04
影响因子：
11.1
作者：
Mao, Albert H.;Crick, Scott L.;Pappu, Rohit V.
通讯作者：
Pappu, Rohit V.
影响因子：
5.3
作者：
Díaz-Hernández, M;Moreno-Herrero, F;Lucas, JJ
通讯作者：
Lucas, JJ
影响因子：
64.5
作者：
Ordway, JM;TallaksenGreene, S;Detloff, PJ
通讯作者：
Detloff, PJ
影响因子：
2.9
作者：
Chen, SM;Berthelier, V;Wetzel, R
通讯作者：
Wetzel, R