Many proteins involved in signal transduction contain peptide recognition modules (PRMs) that recognize short linear motifs (SLiMs) within their interaction partners. Here, we used large‐scale peptide‐phage display methods to derive optimal ligands for 163 unique PRMs representing 79 distinct structural families. We combined the new data with previous data that we collected for the large SH3, PDZ, and WW domain families to assemble a database containing 7,984 unique peptide ligands for 500 PRMs representing 82 structural families. For 74 PRMs, we acquired enough new data to map the specificity profiles in detail and derived position weight matrices and binding specificity logos based on multiple peptide ligands. These analyses showed that optimal peptide ligands resembled peptides observed in existing structures of PRM‐ligand complexes, indicating that a large majority of the phage‐derived peptides are likely to target natural peptide‐binding sites and could thus act as inhibitors of natural protein–protein interactions. The complete dataset has been assembled in an online database (http://www.prm‐db.org) that will enable many structural, functional, and biological studies of PRMs and SLiMs.

中文翻译：

---

肽识别模块高亲和力配体的大规模调查和数据库

许多参与信号转导的蛋白质都含有肽识别模块 (PRM)，可识别其相互作用伙伴内的短线性基序 (SLiM)。在这里，我们使用大规模肽噬菌体展示方法来为代表 79 个不同结构家族的 163 个独特的 PRM 获得最佳配体。我们将新数据与之前为大型 SH3、PDZ 和 WW 结构域家族收集的数据结合起来，构建了一个数据库，其中包含代表 82 个结构家族的 500 个 PRM 的 7,984 个独特肽配体。对于 74 个 PRM，我们获得了足够的新数据来详细绘制特异性图谱，并基于多个肽配体导出位置权重矩阵和结合特异性标志。这些分析表明，最佳肽配体类似于在 PRM 配体复合物的现有结构中观察到的肽，这表明绝大多数噬菌体衍生的肽可能以天然肽结合位点为目标，因此可以充当天然蛋白质-蛋白质的抑制剂互动。完整的数据集已汇集在在线数据库 (http://www.prm-db.org) 中，该数据库将使 PRM 和 SLiM 的许多结构、功能和生物学研究成为可能。