Characterization of intrinsically disordered proteins with electrospray ionization mass spectrometry: conformational heterogeneity of alpha-synuclein.
Characterization of intrinsically disordered proteins with electrospray ionization mass spectrometry: conformational heterogeneity of alpha-synuclein.
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DOI：
10.1002/prot.22604
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发表时间：
2010-02-15
期刊：
影响因子：
2.9
通讯作者：
Kaltashov IA
中科院分区：
文献类型：
--
作者：
Frimpong AK;Abzalimov RR;Uversky VN;Kaltashov IA
通过分析蛋白质离子的电荷态分布，用电喷雾电离质谱仪研究了α-突触核蛋白的构象不均一性，其中多次带电的程度反映了蛋白质在溶液中构象的致密性。虽然α-突触核蛋白在生理条件下缺乏单一明确的结构，但它被发现可以采样四种不同的构象状态，从高度结构的构象到随机卷曲。α-突触核蛋白以致密的高度结构状态存在于所测试的整个条件范围内(pH值从2.5到10，酒精含量从0到60%)，但在酸性溶液中尤其丰富。唯一存在于酸性溶液中的另一种蛋白质状态是部分折叠的中间状态，缺乏稳定的三级结构。另一种更紧密的中间状态是由大量用作共溶剂的乙醇诱导的，似乎代表了具有高β-Sheet含量的部分折叠构象。虽然只有酸性溶液有利于形成高度结构的α-突触核蛋白二聚体，但在整个测试条件下都可以观察到蛋白质二聚体的形成。这些二聚体可能是蛋白质聚集的最早阶段，导致球状低聚物，并随后形成原纤维。
Conformational heterogeneity of α-synuclein was studied with electrospray ionization mass spectrometry by analyzing protein ion charge state distributions, where the extent of multiple charging reflects compactness of the protein conformations in solution. While α-synuclein lacks a single well-defined structure under physiological conditions, it was found to sample four distinct conformational states, ranging from a highly structured one to a random coil. The compact highly structured state of α-synuclein is present across the entire range of conditions tested (pH ranging from 2.5 to 10, alcohol content from 0 to 60%), but is particularly abundant in acidic solutions. The only other protein state populated in acidic solutions is a partially folded intermediate state lacking stable tertiary structure. Another, more compact intermediate state is induced by significant amounts of ethanol used as a co-solvent and appears to represent a partially folded conformation with high β-sheet content. Protein dimerization is observed throughout the entire range of conditions tested, although only acidic solutions favor formation of highly structured dimers of α-synuclein. These dimers are likely to present the earliest stages in protein aggregation leading to globular oligomers and, subsequently, protofibrils.
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影响因子：
7.4
作者：
Abzalimov, Rinat R.;Dubin, Paul L.;Kaltashov, Igor A.
通讯作者：
Kaltashov, Igor A.
影响因子：
6.8
作者：
Eliezer, David
通讯作者：
Eliezer, David
影响因子：
1.6
作者：
Dobson, CM
通讯作者：
Dobson, CM
影响因子：
7.4
作者：
Gumerov, DR;Kaltashov, IA
通讯作者：
Kaltashov, IA
DOI：
10.1021/jp801175w
发表时间：
2008-09-04
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Grabenauer M;Bernstein SL;Lee JC;Wyttenbach T;Dupuis NF;Gray HB;Winkler JR;Bowers MT
通讯作者：
Bowers MT