Ren Siyuan, Uversky Vladimir N, Chen Zhengjun, Dunker A Keith, Obradovic Zoran
Center for Information Science and Technology, Temple University, Philadelphia, PA 19122, USA.
BMC Genomics. 2008 Sep 16;9 Suppl 2(Suppl 2):S26. doi: 10.1186/1471-2164-9-S2-S26.
Protein interactions are essential for most cellular functions. Interactions mediated by domains that appear in a large number of proteins are of particular interest since they are expected to have an impact on diversities of cellular processes such as signal transduction and immune response. Many well represented domains recognize and bind to primary sequences less than 10 amino acids in length called Short Linear Motifs (SLiMs).
In this study, we systematically studied the evolutionary conservation of SLiMs recognized by SH2, SH3 and Ser/Thr Kinase domains in both ordered and disordered protein regions. Disordered protein regions are protein sequences that lack a fixed three-dimensional structure under putatively native conditions. We find that, in all these domains examined, SLiMs are more conserved in disordered regions. This trend is more evident in those protein functional groups that are frequently reported to interact with specific domains.
The correlation between SLiM conservation with disorder prediction demonstrates that functional SLiMs recognized by each domain occur more often in disordered as compared to structured regions of proteins.
蛋白质相互作用对大多数细胞功能至关重要。由大量蛋白质中出现的结构域介导的相互作用尤其令人感兴趣，因为它们预计会对细胞过程的多样性产生影响，如信号转导和免疫反应。许多代表性良好的结构域识别并结合长度小于10个氨基酸的一级序列，称为短线性基序（SLiMs）。
在本研究中，我们系统地研究了SH2、SH3和丝氨酸/苏氨酸激酶结构域在有序和无序蛋白质区域中识别的SLiMs的进化保守性。无序蛋白质区域是指在假定的天然条件下缺乏固定三维结构的蛋白质序列。我们发现，在所有这些研究的结构域中，SLiMs在无序区域中更保守。这种趋势在那些经常被报道与特定结构域相互作用的蛋白质功能组中更为明显。
SLiM保守性与无序预测之间的相关性表明，与蛋白质的结构化区域相比，每个结构域识别的功能性SLiMs在无序区域中出现的频率更高。
