G protein-coupled receptors show unusual patterns of intrinsic unfolding
G protein-coupled receptors show unusual patterns of intrinsic unfolding
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DOI：
10.1093/protein/gzi004
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发表时间：
2005-02-01
影响因子：
2.4
通讯作者：
Goldman, A
中科院分区：
文献类型：
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作者：
Jaakola, VP;Prilusky, J;Goldman, A
固有非结构蛋白(IUP)或IUP样区通常在从转录到细胞周期的控制过程中发挥关键作用。在电子计算机中，这类蛋白质可以通过它们的序列特性来识别；它们具有低疏水性和高净电荷。在这项研究中，我们应用FoldIndex(http://bioportal.weizmann.ac.il/fldbin/findex)程序分析了人G蛋白偶联受体，并将其与已知结构的膜蛋白和IUPS进行了比较。我们发现，与已知结构的膜蛋白不同，人类G蛋白偶联受体(GPCR)膜外域包括长的(>；50个残基)无序片段。预测的失序主要发生在N端、C端和第三胞内区：分别有55%、69%和56%的人GPCR在这些区域失序。因此，这种增加的灵活性可能是GPCR功能的关键。然而，令人惊讶的是，在GPCR非结构化区域中使用的残基种类与迄今已识别的IUPS中使用的残基种类不同。GPCR胞内第三环结构域含有很高比例的Arg、Lys和His残基，尤其是Arg，但Glu、Asp和Pro的比例并不高于折叠蛋白。我们认为，这具有结构性和功能性后果。
Intrinsically unstructured proteins (IUPs) or IUP-like regions often play key roles in controlling processes ranging from transcription to the cell cycle. In silico such proteins can be identified by their sequence properties; they have low hydrophobicity and high net charge. In this study, we applied the FoldIndex (http://bioportal.weizmann.ac.il/fldbin/findex) program to analyze human G protein-coupled receptors and compared them with membrane proteins of known structure and with IUPs. We show that human G protein-coupled receptor (GPCR) extramembranous domains include long (>50 residues) disordered segments, unlike membrane proteins of known structure. The predicted disorder occurred primarily in the N-terminal, C-terminal and third intracellular domain regions: 55, 69 and 56% of the human GPCRs were disordered in these regions, respectively. This increased flexibility may therefore be critical for GPCR function. Surprisingly, however, the kinds of residues used in GPCR unstructured regions were different than in hitherto-identified IUPs. The GPCR third intracellular loop domains contain very high percentages of Arg, Lys and His residues, especially Arg, but the percentage of Glu, Asp and Pro is no higher than in folded proteins. We propose that this has structural and functional consequences.