Propagating structure of Alzheimer's β-amyloid(10-35) is parallel β-sheet with residues in exact register
Propagating structure of Alzheimer's β-amyloid(10-35) is parallel β-sheet with residues in exact register
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DOI：
10.1073/pnas.95.23.13407
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发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
Meredith, SC
中科院分区：
文献类型：
--
作者：
Benzinger, TLS;Gregory, DM;Meredith, SC
阿尔茨海默病的特异性斑块主要由39- 43-aa的β-淀粉样蛋白（A β）肽组成。通过组织转氨酶（tTg）交联A β肽表明在聚集的A β中一种肽的Gln（15）接近另一种肽的Lys（16）。sere se报道了如何通过用固态NMR绘制A β肽链核心区域的链间距离来解析原纤维结构。同位素替代提供了测量聚集A β中距离的源点。合成在Gln 15、Lys（16）、Leu（17）或瓦尔（18）处含有单个羰基C-13标记的肽，并通过NMR偶极再偶联方法进行评价，以测量肽间距离，分辨率为0.2埃。对这些数据的分析表明，A β的中心核心由平行的β折叠结构组成，其中相邻链上的相同残基直接对齐，即，在注册。我们的数据！结合现有的结构数据，确定A β原纤维是一种氢键结合的平行β-折叠，定义了A β原纤维增长的长轴。
The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa beta-amyloid (A beta) peptide. Crosslinking of A beta peptides by tissue transglutaminase (tTg) indicates that Gln(15) of one peptide is proximate to Lys(16) of another in aggregated A beta. sere se report how the fibril structure is resolved by mapping interstrand distances in this core region of the A beta peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated A beta. Peptides containing a single carbonyl C-13 label at Gln15, Lys(16), Leu(17), Or Val(18) were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 Angstrom. Analysis of these data establish that this central core of A beta consists of a parallel beta-sheet structure in which identical residues on adjacent chains are aligned directly, i,e., in register. Our data! in conjunction with existing structural data, establish that the A beta fibril is a hydrogen-bonded, parallel beta-sheet defining the long asis of the A beta fibril propagation.