Pleckstrin homology (PH) domains and phosphoinositides
Pleckstrin homology (PH) domains and phosphoinositides
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DOI：
10.1042/bss2007c08
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发表时间：
2007-01-01
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影响因子：
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通讯作者：
Lemmon, Mark A.
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文献类型：
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作者：
Lemmon, Mark A.
PH（普列克底物蛋白同源性）结构域代表人类蛋白质组中第11个最常见的结构域。它们以其以高亲和力和特异性结合磷酸肌醇的能力而闻名，尽管现在清楚的是，所有PH结构域中只有不到10%具有这种特性。PH结构域以高亲和力结合特异性磷酸肌醇的情况限于在其肌醇头基中具有一对相邻磷酸的那些磷酸肌醇。那些没有的[PtdIns 3 P、PtdIns 5 P和PtdIns（3，5）P]反而被不同类别的结构域识别，包括FYVE结构域、PX（phox同源）结构域、PHD（植物同源结构域）指和最近鉴定的PROPPIN（结合聚磷酸肌醇的P-推进器）。90%的PH结构域不强烈和特异性地结合磷酸肌醇，很少有人很好地理解。一组PH结构域似乎结合磷酸肌醇（具有很小的特异性）和Arf（ADP-核糖基化因子）家族小G蛋白，并靶向高尔基体，其中磷酸肌醇和相关的Arf都存在。这里，PH域可以用作符合检测器。理解大多数PH结构域的一个核心挑战是确定在许多情况下报道的非常低亲和力的磷酸肌醇结合是否具有任何功能相关性。对于来自发动蛋白和Dbl家族蛋白的PH结构域，这种弱结合似乎在功能上是重要的，尽管其精确的机制作用尚不清楚。在许多其他情况下，很可能替代结合配偶体更相关，并且观察到的PH结构域同源性代表结构折叠而不是功能的保守性。
PH (pleckstrin homology) domains represent the 11th most common domain in the human proteome. They are best known for their ability to bind phosphoinositides with high affinity and specificity, although it is now clear that less than 10% of all PH domains share this property. Cases in which PH domains bind specific phosphoinositides with high affinity are restricted to those phosphoinositides that have a pair of adjacent phosphates in their inositol headgroup. Those that do not [PtdIns3P, PtdIns5P and PtdIns(3,5)P,] are instead recognized by distinct classes of domains including FYVE domains, PX (phox homology) domains, PHD (plant homeodomain) fingers and the recently identified PROPPINs (P-propellers that bind polyphosphoinositides). Of the 90% of PH domains that do not bind strongly and specifically to phosphoinositides, few are well understood. One group of PH domains appears to bind both phosphoinositides (with little specificity) and Arf (ADP-ribosylation factor) family small G-proteins, and are targeted to the Golgi apparatus where both phosphoinositides and the relevant Arfs are both present. Here, the PH domains may function as coincidence detectors. A central challenge in understanding the majority of PH domains is to establish whether the very low affinity phosphoinositide binding reported in many cases has any functional relevance. For PH domains from dynamin and from Dbl family proteins, this weak binding does appear to be functionally important, although its precise mechanistic role is unclear. In many other cases, it is quite likely that alternative binding partners are more relevant, and that the observed PH domain homology represents conservation of structural fold rather than function.