NACP, THE PRECURSOR PROTEIN OF THE NONAMYLOID BETA/A4 PROTEIN (A-BETA) COMPONENT OF ALZHEIMER-DISEASE AMYLOID, BINDS A-BETA AND STIMULATES A-BETA AGGREGATION
NACP, THE PRECURSOR PROTEIN OF THE NONAMYLOID BETA/A4 PROTEIN (A-BETA) COMPONENT OF ALZHEIMER-DISEASE AMYLOID, BINDS A-BETA AND STIMULATES A-BETA AGGREGATION
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DOI：
10.1073/pnas.92.20.9141
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发表时间：
1995-09-26
影响因子：
11.1
通讯作者：
SAITOH, T
中科院分区：
文献类型：
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作者：
YOSHIMOTO, M;IWAI, A;SAITOH, T
NACP是一种140个氨基酸的突触前蛋白，是NAC [阿尔茨海默病（AD）淀粉样蛋白的非淀粉样蛋白β/A4蛋白（A β）组分]的前体，NAC是一种从患有AD的患者的脑淀粉样蛋白中分离并免疫学定位于其上的肽，大肠杆菌中产生的NACP与A β肽结合，A β肽是AD淀粉样蛋白的主要组分，NACP与固定在硝酸纤维素上的A β 1-38和A β 25-35结合，但在相同条件下不与滤器上的A β 1-28结合。NACP与A β 1-38的结合通过添加A β 25-35而被消除，但不通过A β 1-28，表明A β肽的疏水区域对这种结合至关重要。NACP-112，一种含有NAC序列的NACP的较短剪接变体，与A β结合，但NACP δ，一种缺乏NAC结构域的NACP缺失突变体，不与A β 1-38结合。此外，NACP-112和A β 1-38之间的结合通过添加肽Y而降低，肽Y是覆盖NAC的最后15个残基的肽。在水溶液中，当NACP也以1：125（NACP/A β）的比例存在于孵育混合物中时，观察到A β 1-38聚集，而单独的A β 1-38或单独的NACP在相同条件下不聚集，这表明A β和NACP之间形成复合物可能促进AP的聚集。因此，NACP可以通过特定序列结合A β肽，并可以促进A β聚集，提高了NACP可能在AD淀粉样蛋白的发展中发挥作用的可能性。
NACP, a 140-amino acid presynaptic protein, is the precursor of NAC [the non-amyloid beta/A4 protein (A beta) component of Alzheimer disease (AD) amyloid], a peptide isolated from and immunologically localized to brain amyloid of patients afflicted with AD, NACP produced in Escherichia coli bound to A beta peptides, the major component of AD amyloid, NACP bound to A beta 1-38 and A beta 25-35 immobilized on nitrocellulose but did not bind to A beta 1-28 on the filter under the same conditions. NACP binding to A beta 1-38 was abolished by addition of A beta 25-35 but not by A beta 1-28, suggesting that the hydrophobic region of the A beta peptide is critical to this binding. NACP-112, a shorter splice variant of NACP containing the NAC sequence, bound to A beta, but NACP delta, a deletion mutant of NACP lacking the NAC domain, did not bind A beta 1-38. Furthermore, binding between NACP-112 and A beta 1-38 was decreased by addition of peptide Y, a peptide that covers the last 15 residues of NAC. In an aqueous solution, A beta 1-38 aggregation was observed when NACP was also present in an incubation mixture at a ratio of 1:125 (NACP/A beta), whereas A beta 1-38 alone or NACP alone did not aggregate under the same conditions, suggesting that the formation of a complex between A beta and NACP may promote aggregation of AP. Thus, NACP can bind A beta peptides through the specific sequence and can promote A beta aggregation, raising the possibility that NACP may play a role in the development of AD amyloid.