Protein origami: therapeutic rescue of misfolded gene products.
Protein origami: therapeutic rescue of misfolded gene products.
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DOI：
10.1124/mi.2.5.308
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发表时间：
2002-09-01
影响因子：
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通讯作者：
Janovick, Jo Ann
中科院分区：
文献类型：
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作者：
Conn, P Michael;Leanos-Miranda, Alfredo;Janovick, Jo Ann
引起功能丧失的受体突变有时等同于消除受体-配体结合或受体-效应物相互作用的缺陷。类似地，突变缺陷的酶和离子通道通常被视为分别在底物或离子识别中受损。然而，最近的观察表明，另一种机制可能令人惊讶地普遍，即结构基因中的突变可能不干扰受影响蛋白质的固有功能，但仍然通过阻止细胞的运输机制将受影响蛋白质置于适当的亚细胞区室（例如，细胞膜）。因此，可以设计治疗以确保受体（或其他蛋白质）放置在它们可以支持细胞功能的位置。
Receptor mutations that elicit loss of function are sometimes equated with defects that ablate receptor-ligand binding or receptor-effector interactions. Similarly, mutationally defective enzymes and ion channels are often viewed as compromised in substrate or ion recognition, respectively. Recent observations, however, suggest that an alternate mechanism may be surprisingly common, namely, that mutations in structural genes may not interfere with the inherent functionality of the affected protein, but nevertheless cause disease by preventing the cell's trafficking machinery from placing the affected protein at the appropriate subcellular compartment (e.g., at the cell membrane). Accordingly, therapies may be devised to ensure the placement of receptors (or other proteins) at locations where they can support cell function.