High-throughput methods for identification of protein-protein interactions involving short linear motifs.
High-throughput methods for identification of protein-protein interactions involving short linear motifs.
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DOI：
10.1186/s12964-015-0116-8
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发表时间：
2015-08-22
期刊：
影响因子：
--
通讯作者：
Ivarsson Y
中科院分区：
文献类型：
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作者：
Blikstad C;Ivarsson Y
模块结构域和短线性基序（3-10个氨基酸肽延伸）之间的相互作用对细胞信号传导至关重要。基序通常位于蛋白质组的无序区域，相互作用通常是短暂的，允许对变化的刺激作出快速变化。使结构域-基序相互作用适合细胞信号传导的特性也使它们难以在实验中捕获，因此在已知的蛋白质-蛋白质相互作用网络中它们在很大程度上未被充分代表。尽管存在专门的高通量方法来识别结构域-基序相互作用，但大多数关于结构域-基序相互作用的知识都来自低通量研究。这些方法包括多肽或蛋白质的阵列，多肽在噬菌体或酵母上的展示，以及酵母-双杂交实验。我们在这里提供了一个可扩展的方法领域-基序相互作用分析的调查。这些方法经常被应用于有限数量的普遍存在的领域族。现在是时候将它们应用于更广泛的肽结合蛋白，提供人类蛋白质组中线性基序的全面图像，并将它们与潜在的结合伙伴联系起来。尽管方法繁多，但对于大多数方法来说，确定依赖于翻译后修饰或上下文依赖或条件相互作用的相互作用仍然是一个挑战，这为进一步的方法发展提出了方向。
Interactions between modular domains and short linear motifs (3–10 amino acids peptide stretches) are crucial for cell signaling. The motifs typically reside in the disordered regions of the proteome and the interactions are often transient, allowing for rapid changes in response to changing stimuli. The properties that make domain-motif interactions suitable for cell signaling also make them difficult to capture experimentally and they are therefore largely underrepresented in the known protein-protein interaction networks. Most of the knowledge on domain-motif interactions is derived from low-throughput studies, although there exist dedicated high-throughput methods for the identification of domain-motif interactions. The methods include arrays of peptides or proteins, display of peptides on phage or yeast, and yeast-two-hybrid experiments. We here provide a survey of scalable methods for domain-motif interaction profiling. These methods have frequently been applied to a limited number of ubiquitous domain families. It is now time to apply them to a broader set of peptide binding proteins, to provide a comprehensive picture of the linear motifs in the human proteome and to link them to their potential binding partners. Despite the plethora of methods, it is still a challenge for most approaches to identify interactions that rely on post-translational modification or context dependent or conditional interactions, suggesting directions for further method development.