Boulanger Martin J, Bankovich Alexander J, Kortemme Tanja, Baker David, Garcia K Christopher
Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305, USA.
Mol Cell. 2003 Sep;12(3):577-89. doi: 10.1016/s1097-2765(03)00365-4.
Gp130 is a shared cell-surface signaling receptor for at least ten different hematopoietic cytokines, but the basis of its degenerate recognition properties is unknown. We have determined the crystal structure of human leukemia inhibitory factor (LIF) bound to the cytokine binding region (CHR) of gp130 at 2.5 A resolution. Strikingly, we find that the shared binding site on gp130 has an entirely rigid core, while the LIF binding interface diverges sharply in structure and chemistry from that of other gp130 ligands. Dissection of the LIF-gp130 interface, along with comparative studies of other gp130 cytokines, reveal that gp130 has evolved a "thermodynamic plasticity" that is relatively insensitive to ligand structure, to enable crossreactivity. These observations reveal a novel and alternative mechanism for degenerate recognition from that of structural plasticity.
gp130是至少十种不同造血细胞因子的共同细胞表面信号受体，但其简并识别特性的基础尚不清楚。我们已经确定了与gp130的细胞因子结合区域（CHR）结合的人白血病抑制因子（LIF）的晶体结构，分辨率为2.5埃。令人惊讶的是，我们发现gp130上的共享结合位点有一个完全刚性的核心，而LIF结合界面在结构和化学性质上与其他gp130配体有很大差异。对LIF-gp130界面的剖析以及对其他gp130细胞因子的比较研究表明，gp130已经进化出一种对配体结构相对不敏感的“热力学可塑性”，以实现交叉反应。这些观察结果揭示了一种与结构可塑性不同的简并识别新机制。
