A novel peptide-SH3 interaction
A novel peptide-SH3 interaction
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DOI：
10.1093/emboj/18.19.5300
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发表时间：
1999-10-01
期刊：
影响因子：
11.4
通讯作者：
Di Fiore, PP
中科院分区：
文献类型：
--
作者：
Mongiovi, AM;Romano, PR;Di Fiore, PP
SH3 结构域构成了一系列蛋白质-蛋白质相互作用模块，可与显示 X-脯氨酸-X-X-脯氨酸 (XXXXP) 共有序列的肽结合。我们报告说，Eps8 的 SH3 结构域（受体和非受体酪氨酸激酶的底物）表现出新颖且独特的结合偏好。通过组合方法，包括（i）筛选噬菌体展示的随机肽库，（ii）Eps8的三个生理相互作用物上的结合区域图谱，（iii）结合肽的丙氨酸扫描和（iv）体外交联，我证明脯氨酸-X-X-天冬氨酸-酪氨酸（PXXDY）共有序列对于与Eps8的SH3结构域的结合是必不可少的，表达序列标签数据库的筛选允许鉴定三个Eps8 相关基因，其 SH3 也表现出不寻常的结合偏好，并构成 SH3 家族中系统发育上不同的亚家族。因此，Eps8 鉴定了一个新的包含 SH3 的蛋白质家族，该家族不与典型的包含 XPXXP 的肽结合，并在信号网络中建立了独特的相互作用。
SH3 domains constitute a family of protein-protein interaction modules that bind to peptides displaying an X-proline-X-X-proline (XPXXP) consensus. We report that the SH3 domain of Eps8, a substrate of receptor and non-receptor tyrosine kinases, displays a novel and unique binding preference. By a combination of approaches including (i) screening of phage-displayed random peptide libraries, (ii) mapping of the binding regions on three physiological interactors of Eps8, (iii) alanine scanning of binding peptides and (iv) in vitro cross-linking, me demonstrate that a proline-X-X-aspartate-tyrosine (PXXDY) consensus is indispensable for binding to the SH3 domain of Eps8, Screening of the Expressed Sequence Tags database allowed the identification of three Eps8-related genes, whose SH3s also display unusual binding preferences and constitute a phylogenetically distinct subfamily within the SH3 family, Thus, Eps8 identifies a novel family of SH3-containing proteins that do not bind to canonical XPXXP-containing peptides, and that establish distinct interactions in the signaling network.