Hopp T P
Protein Research Laboratories, Inc., San Diego, California 92126, USA.
Protein Sci. 1995 Sep;4(9):1851-9. doi: 10.1002/pro.5560040920.
Evidence is presented that the cytoplasmic domain of the type I interleukin-1 receptor (IL-1R) may be a GTPase. This domain conserves segments of hydrophobic amino acids that suggest a structural relatedness to the ras protooncogene protein and other members of the GTPase superfamily, despite a lack of significant detectable sequence homology. When the hydrophobic segments of the IL-1R were aligned with similar segments of the GTPases, it became apparent that the IL-1Rs possess a number of conserved amino acids that represent plausible functional residues for base-specific binding of GTP, magnesium chelation, and phosphate ester hydrolysis. Furthermore, a segment of five contiguous residues were found that is identical between ras and the IL-1R, and which is positioned to form part of the guanine base binding pocket. If this model is correct, then the IL-1Rs possess a highly conserved effector protein binding region, but one that is entirely unrelated to the effector regions of other superfamily members. Therefore, if the IL-1R is indeed a GTPase, then its activation function may be directed to as-yet unrecognized effector target proteins, as part of a unique cellular signal transduction pathway.
有证据表明，I型白细胞介素-1受体（IL-1R）的胞质结构域可能是一种GTP酶。尽管缺乏明显可检测到的序列同源性，但该结构域保留了疏水氨基酸片段，这表明它与ras原癌基因蛋白及GTP酶超家族的其他成员在结构上具有相关性。当将IL-1R的疏水片段与GTP酶的类似片段进行比对时，很明显IL-1R拥有一些保守氨基酸，它们可能是与GTP进行碱基特异性结合、镁螯合及磷酸酯水解的功能性残基。此外，发现了一段由五个相邻残基组成的片段，它在ras和IL-1R之间是相同的，并且定位形成鸟嘌呤碱基结合口袋的一部分。如果这个模型是正确的，那么IL-1R拥有一个高度保守的效应蛋白结合区域，但该区域与其他超家族成员的效应区域完全无关。因此，如果IL-1R确实是一种GTP酶，那么其激活功能可能针对尚未被识别的效应靶蛋白，作为独特细胞信号转导途径的一部分。
