Structural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding.

IF 2.2 4区生物学 Acta Crystallographica Section D: Biological Crystallography Pub Date : 2015-11-01 Epub Date: 2015-10-31 DOI:10.1107/S1399004715018015

Vaheh Oganesyan, Yariv Mazor, Chunning Yang, Kimberly E Cook, Robert M Woods, Andrew Ferguson, Michael A Bowen, Tom Martin, Jie Zhu, Herren Wu, William F Dall'Acqua

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引用次数: 21

Abstract

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.

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人类IgG1与fc - γ - ri相互作用的结构见解:聚糖在结合中没有直接作用。

报道了与野生型人Fcγ ri结合的人IgG1 Fc片段的三维结构。采用分子置换法以2.4 Å的分辨率解析相应配合物的结构;这是未突变的FcγRI分子的最高分辨率。本研究强调了fc γ - ri的第二胞外亚域在结构和功能上的关键作用。它还通过“锁与钥匙”机制解释了234-237位Fc ' LLGG'基序的主要能量贡献，特别是Leu235。最后，更正了先前持有的观点，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供了不同的观点。结构证据表明，这种与聚糖相关的影响是严格间接的。

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来源期刊

Acta Crystallographica Section D: Biological Crystallography 生物-晶体学

自引率

13.60%

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审稿时长

3 months

期刊介绍： Acta Crystallographica Section D welcomes the submission of articles covering any aspect of structural biology, with a particular emphasis on the structures of biological macromolecules or the methods used to determine them. Reports on new structures of biological importance may address the smallest macromolecules to the largest complex molecular machines. These structures may have been determined using any structural biology technique including crystallography, NMR, cryoEM and/or other techniques. The key criterion is that such articles must present significant new insights into biological, chemical or medical sciences. The inclusion of complementary data that support the conclusions drawn from the structural studies (such as binding studies, mass spectrometry, enzyme assays, or analysis of mutants or other modified forms of biological macromolecule) is encouraged. Methods articles may include new approaches to any aspect of biological structure determination or structure analysis but will only be accepted where they focus on new methods that are demonstrated to be of general applicability and importance to structural biology. Articles describing particularly difficult problems in structural biology are also welcomed, if the analysis would provide useful insights to others facing similar problems.

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