Naismith J H, Brandhuber B J, Devine T Q, Sprang S R
Centre for Biomolecular Sciences, University of St. Andrews, Fife, Scotland, UK.
J Mol Recognit. 1996 Mar-Apr;9(2):113-7. doi: 10.1002/(sici)1099-1352(199603)9:2<113::aid-jmr253>3.0.co;2-h.
The crystal structure of the extracellular domain of the type I tumor necrosis factor receptor (sTNF-R1) has been determined to 2.25 A at pH 7.5. We have also solved the structure of sTNF-R1 at pH 3.7. sTNF-R1 is an elongated molecule consisting of a linear combination of four cysteine-rich motifs. Interestingly, the crystal structure reveals two distinct dimers of the receptor. One dimer is formed by a parallel arrangement of receptors, the other by an antiparallel arrangement of receptors. In the parallel arrangement of the receptors, the tumor necrosis factor (TNF) binding face of the receptor is completely exposed to solvent. However, in the antiparallel arrangement, the TNF binding face is intimately involved in the dimer interactions. Details of these recognition surfaces are discussed. Both these dimer interactions bury substantial surface area, comprise polar and apolar contact surfaces and have complimentary recognition surfaces. Thus these interactions are typical of genuine protein-protein interactions, rather than crystal packing contacts. These dimers may function to inhibit signal transduction in the absence of TNF or in the case of the parallel dimer, promote clustering of TNF/TNF receptor complexes on the cell surface.
I型肿瘤坏死因子受体（sTNF-R1）胞外域的晶体结构在pH 7.5时已确定为2.25埃。我们还解析了pH 3.7时sTNF-R1的结构。sTNF-R1是一个由四个富含半胱氨酸基序线性组合而成的细长分子。有趣的是，晶体结构揭示了受体的两种不同二聚体。一种二聚体由受体的平行排列形成，另一种由受体的反平行排列形成。在受体的平行排列中，受体的肿瘤坏死因子（TNF）结合面完全暴露于溶剂中。然而，在反平行排列中，TNF结合面密切参与二聚体相互作用。讨论了这些识别表面的细节。这两种二聚体相互作用都掩埋了大量表面积，包含极性和非极性接触表面，并具有互补的识别表面。因此，这些相互作用是典型的真实蛋白质-蛋白质相互作用，而不是晶体堆积接触。这些二聚体可能在没有TNF的情况下起到抑制信号转导的作用，或者在平行二聚体的情况下，促进TNF/TNF受体复合物在细胞表面的聚集。
