Oganesyan Vaheh, Mazor Yariv, Yang Chunning, Cook Kimberly E, Woods Robert M, Ferguson Andrew, Bowen Michael A, Martin Tom, Zhu Jie, Wu Herren, Dall'Acqua William F
Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
Discovery Sciences, Structure and Biophysics, AstraZeneca Pharmaceuticals, 35 Gatehouse Drive, Mailstop E3, Waltham, MA 02451, USA.
Acta Crystallogr D Biol Crystallogr. 2015 Nov;71(Pt 11):2354-61. doi: 10.1107/S1399004715018015. Epub 2015 Oct 31.
The three-dimensional structure of a human IgG1 Fc fragment bound to wild-type human FcγRI is reported. The structure of the corresponding complex was solved at a resolution of 2.4 Å using molecular replacement; this is the highest resolution achieved for an unmutated FcγRI molecule. This study highlights the critical structural and functional role played by the second extracellular subdomain of FcγRI. It also explains the long-known major energetic contribution of the Fc LLGG' motif at positions 234-237, and particularly of Leu235, via a lock-and-key' mechanism. Finally, a previously held belief is corrected and a differing view is offered on the recently proposed direct role of Fc carbohydrates in the corresponding interaction. Structural evidence is provided that such glycan-related effects are strictly indirect.
报道了与野生型人FcγRI结合的人IgG1 Fc片段的三维结构。使用分子置换法以2.4 Å的分辨率解析了相应复合物的结构；这是未突变的FcγRI分子所达到的最高分辨率。这项研究突出了FcγRI第二个细胞外亚结构域所起的关键结构和功能作用。它还通过“锁钥”机制解释了Fc在234-237位的“LLGG”基序，特别是Leu235长期以来已知的主要能量贡献。最后，纠正了之前的一种观点，并对最近提出的Fc碳水化合物在相应相互作用中的直接作用提出了不同看法。提供了结构证据表明这种与聚糖相关的效应是严格间接的。
