Protein misfolding, evolution and disease
Protein misfolding, evolution and disease
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DOI：
10.1016/s0968-0004(99)01445-0
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发表时间：
1999-09-01
影响因子：
13.8
通讯作者：
Dobson, CM
中科院分区：
文献类型：
--
作者：
Dobson, CM
图1球状蛋白形成淀粉样纤维的可能机制示意图。在核糖体上合成后，蛋白质被认为在内质网（ER）中折叠，分子伴侣有助于阻止不完全折叠物质的聚集。正确折叠的蛋白质从细胞中分泌出来，并在其细胞外环境中正常发挥功能。在某些条件下，蛋白质至少部分地展开，并且变得易于聚集。这可导致形成积聚在组织中的原纤维和其他聚集体。小聚集体以及高度组织化的原纤维和斑块可能至少在某些情况下引起病理状况。N、I和U分别指蛋白质的天然、部分折叠（中间）和未折叠状态。QC是指防止不完全折叠的蛋白质从内质网分泌的质量控制机制35。
Figure 1 Schematic representation of the possible mechanism of formation of amyloid fibrils by a globular protein. After synthesis on the ribosome, the protein is assumed to fold in the endoplasmic reticulum (ER), aided by molecular chaperones that deter aggregation of incompletely folded species. The correctly folded protein is secreted from the cell and functions normally in its extracellular environment. Under certain conditions the protein unfolds, at least partially, and becomes prone to aggregation. This can result in the formation of fibrils and other aggregates that accumulate in tissue. It is likely that small aggregates, as well as the highly organized fibrils and plaques, can give rise to pathological conditions in at least some cases. N, I and U refer to native, partially folded (intermediate) and unfolded states of the protein, respectively. QC refers to the quality control mechanism that prevents incompletely folded proteins being secreted from the endoplasmic reticulum35.