Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
FEBS Lett. 2012 Jun 21;586(13):1754-8. doi: 10.1016/j.febslet.2012.05.007. Epub 2012 May 15.
Apolipoprotein A-I (apoA-I) is deposited as amyloid within various major organs in hereditary apoA-I amyloidosis, and in arterial plaques associated with atherosclerosis. We have identified a tryptic fragment of apoA-I, apoA-I(46-59), that retains the ability to form amyloid-like fibrils with cross-β structure. ApoA-I(46-59) corresponds closely to a conformationally extended segment in the crystal structure of apoA-IΔ(185-243) and is located in the N-terminal region of apoA-I, which accumulates in hereditary apoA-I amyloidosis. Our results provide direct experimental evidence that this region of apoA-I is amyloidogenic and integral to initiation and propagation of amyloid formation by the protein.
载脂蛋白 A-I（apoA-I）在遗传性载脂蛋白 A-I 淀粉样变性的各种主要器官中和动脉粥样硬化相关的动脉斑块中沉积为淀粉样物质。我们已经鉴定出载脂蛋白 A-I 的一个胰蛋白酶片段，即 apoA-I(46-59)，它仍然具有形成具有交叉-β结构的类淀粉样纤维的能力。apoA-I(46-59)与 apoA-IΔ(185-243)晶体结构中伸展构象的一段非常接近，并且位于载脂蛋白 A-I 的 N 端区域，该区域在遗传性载脂蛋白 A-I 淀粉样变性中积累。我们的研究结果提供了直接的实验证据，证明apoA-I 的这一区域具有淀粉样变性质，是蛋白质起始和传播淀粉样形成的必要组成部分。
