Pocket proteins retinoblastoma (pRb), p107 and p130 are negative regulators of cellular proliferation and multifunctional proteins regulating development, differentiation and chromatin structure. The retinoblastoma protein is a potent tumor suppressor mutated in a wide range of human cancers, and oncogenic viruses often interfere with cell cycle regulation by inactivating pRb. The LxCxE and pRb AB groove short linear motifs (SLiMs) are key to many pocket protein mediated interactions including host and viral partners. A review of available experimental evidence reveals that several core residues composing each motif instance are determinants for binding. In the LxCxE motif, a fourth hydrophobic position that might allow variable spacing is required for binding. In both motifs, flanking regions including charged stretches and phosphorylation sites can fine-tune the binding affinity and specificity of pocket protein SLiM-mediated interactions. Flanking regions can modulate pocket protein binding specificity, or tune the high affinity interactions of viral proteins that hijack the pRb network. The location of SLiMs within intrinsically disordered regions allows faster evolutionary rates that enable viruses to acquire a functional variant of the core motif by convergent evolution, and subsequently test numerous combinations of flanking regions towards maximizing interaction specificity and affinity. This knowledge can guide future efforts directed at the design of peptide-based compounds that can target pocket proteins to regulate the G1/S cell cycle checkpoint or impair viral mediated pRb inactivation.

中文翻译：

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短的线性基序核心和侧翼区域调节成视网膜细胞瘤蛋白的结合亲和力和特异性。

口袋蛋白视网膜母细胞瘤（pRb），p107和p130是细胞增殖的负调节剂，是调节发育，分化和染色质结构的多功能蛋白。视网膜母细胞瘤蛋白是在多种人类癌症中突变的有效的肿瘤抑制因子，致癌病毒通常会通过灭活pRb来干扰细胞周期调控。LxCxE和pRb AB沟短线性基序（SLiMs）是许多口袋蛋白介导的相互作用（包括宿主和病毒伴侣）的关键。对可用实验证据的审查表明，组成每个基序实例的几个核心残基是结合的决定因素。在LxCxE母题中，绑定需要一个可能允许可变间距的第四个疏水位置。在两个主题中 侧翼区域（包括带电的延伸片段和磷酸化位点）可以微调口袋蛋白SLiM介导的相互作用的结合亲和力和特异性。侧翼区域可以调节口袋蛋白的结合特异性，或调节劫持pRb网络的病毒蛋白的高亲和力相互作用。SLiMs在内部无序区域内的位置允许更快的进化速率，使病毒能够通过收敛进化获得核心基序的功能变异，并随后测试侧翼区域的多种组合以最大化相互作用特异性和亲和力。这些知识可以指导未来针对基于肽的化合物设计的工作，这些化合物可以靶向口袋蛋白来调节G1 / S细胞周期检查点或损害病毒介导的pRb失活。