Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains
Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains
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DOI：
10.1002/j.1460-2075.1996.tb00442.x
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发表时间：
1996-03-01
期刊：
影响因子：
11.4
通讯作者：
Leder, P
中科院分区：
文献类型：
--
作者：
Chan, DC;Bedford, MT;Leder, P
参与鼠肢体和肾脏发育的formin蛋白含有与Src同源性3（SH 3）配体的共有序列相匹配的富含脯氨酸的区域。为了鉴定与formin相互作用的蛋白质，我们使用这个富含脯氨酸的区域来筛选小鼠肢芽表达文库中的SH 3结合蛋白（FBPs）。正如预期的那样，我们发现了一类含有SH 3结构域的FBPs，包括这类的两个新成员。此外，然而，我们还发现了一类新的FBPs，它包含一个或两个拷贝的26个氨基酸的同源区域，最近被称为WWP或WW蛾，我们证明，WWP/WW结构域短至26个氨基酸可以作为模块化的蛋白质结合界面，结合与高亲和力的脯氨酸丰富的序列是相似的，在某些情况下，相同的SH 3配体。此外，我们发现WWP/WW结构域可以与Abl SH 3结构域竞争结合存在于大肠杆菌中的富含脯氨酸的肽。我们的研究结果表明，这些新的蛋白质相互作用结构域可以执行类似于SH 3结构域的功能，因此，可能通过竞争性结合调节SH 3与靶蛋白的相互作用。
The formins, proteins involved in murine limb and kidney development, contain a proline-rich region that matches consensus sequences for Src homology 3 (SH3) ligands. To identify proteins that interact with formins, we used this proline-rich region to screen mouse limb bud expression libraries for formin binding proteins (FBPs), As expected, we found one class of FBPs that contains SH3 domains, including two novel members of this class. In addition, however, we also found a novel class of FBPs that contains one or two copies of a 26 amino acid homology region that has been recently termed the WWP or WW moth, We demonstrate that WWP/WW domains as short as 26 amino acids can act as modular protein-binding interfaces that bind with high affinity to proline-rich sequences that are similar and, in some cases, identical to SH3 ligands. Furthermore, we find that the WWP/WW domain can compete with the Abl SH3 domain in binding a proline-rich peptide present in formin. Our results suggest that these novel protein interaction domains can perform functions similar to those of SH3 domains and, thus, might regulate SH3 interactions with target proteins through competitive binding.