tnf - α突变体R31D的晶体结构与受体R1相比具有更高的亲和力。
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Reed C，付志强，吴娟，薛燕，Harrison RW，陈明梅，Weber IT
tnf - α突变体R31D的晶体结构与受体R1相比具有更高的亲和力。
蛋白质学报，1997 10月;10(10):1101-7。
- PubMed ID
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9488135 (PubMed视图］
- 摘要
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已经确定了重组人肿瘤坏死因子- α (TNF- α)及其突变体R31D的晶体结构，该突变体优先与TNF受体R1结合，与受体R2结合的相对亲和力超过7倍。野生型TNF晶体为P4(1)2(1)2空间组，单位细胞尺寸a = b = 94.7, c = 117.4 a。经过结构的改进，在2.5 A分辨率下r因子达到22.3%。突变体TNF R31D晶体衍射分辨率为2.3 A，与野生型具有相同的空间群，单位细胞尺寸A = b = 95.4, c = 116.2 A，结构细化到r因子21.8%。野生型和突变型TNF的三聚体结构相似，Calpha原子的均方根(r.m.s)偏差为0.56 a;然而，每个三聚体中的亚基变化更大，在Calpha原子上的平均r.m.s.偏差为1.00 A。TNF与受体R1和R2的模型复合物已用于预测TNF-受体的相互作用。预计野生型TNF的所有三个亚基中的Arg31在受体R1和R2中与等效的谷氨酸形成离子相互作用。据预测，TNF R31D突变体的Asp31与这两种受体的相互作用不同。TNF突变体的两个亚基中的Asp31侧链被预测与R1的Ser59或Cys70形成氢键相互作用，而与R2没有相互作用。 The loss of three strong ionic interactions of Arg31 and the electrostatic repulsion of Asp31 with Glu in the receptors is consistent with the reduced binding of the R31D mutant to both receptors relative to wild-type TNF. The replacement of these ionic interactions by two weaker hydrogen bond interactions between Asp31 of the R31D mutant and R1, compared with no interactions with R2, is in agreement with the observed preferential binding of the R31D mutant to R1 over R2. Analysis of the structure and function of receptor-discriminating mutants of TNF will help understand the biological role of TNF and facilitate its use as an antitumor agent.