Myoglobin forms amyloid fibrils by association of unfolded polypeptide segments
Myoglobin forms amyloid fibrils by association of unfolded polypeptide segments
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DOI：
10.1073/pnas.0303758100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Diekmann, S
中科院分区：
文献类型：
--
作者：
Fändrich, M;Forge, V;Diekmann, S
B-折叠蛋白在至少部分变性条件下形成淀粉样原纤维的观察结果提出了关于这些原纤维是否通过预形成的B-结构的对接或通过未折叠的多肽片段的缔合而组装的问题。通过使用α-螺旋蛋白脱辅基肌红蛋白，我们表明，容易的原纤维组装与变性的程度。相比之下，在原纤维形成的条件下不能观察到单体β-折叠中间体。这些数据表明，淀粉样原纤维的形成依赖于无序的多肽片段和条件，是选择性地不利于折叠。然而，这是不可避免的，这样的条件往往稳定蛋白质折叠中间体。
Observations that B-sheet proteins form amyloid fibrils under at least partially denaturing conditions has raised questions as to whether these fibrils assemble by docking of preformed B-structure or by association of unfolded polypeptide segments. By using a-helical protein apomyoglobin, we show that the ease of fibril assembly correlates with the extent of denaturation. By contrast, monomeric beta-sheet intermediates could not be observed under the conditions of fibril formation. These data suggest that amyloid fibril formation from apomyoglobin depends on disordered polypeptide segments and conditions that are selectively unfavorable to folding. However, it is inevitable that such conditions often stabilize protein folding intermediates.