Structure and Dynamics of Stacking Interactions in an Antibody Binding Site.
Structure and Dynamics of Stacking Interactions in an Antibody Binding Site.
复制标题
抗体结合位点中堆积相互作用的结构和动力学。
DOI：
10.1021/acs.biochem.9b00119
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Romesberg,FloydE
中科院分区：
文献类型：
--
作者：
Adhikary,Ramkrishna;Zimmermann,Jörg;Stanfield,RobynL;Wilson,IanA;Yu,Wayne;Oda,Masayuki;Romesberg,FloydE
多年来，抗体（Abs）一直被用作理解蛋白质结构如何有助于分子识别的范例。然而，由于能够进化出识别特定发色团的抗体，它们也具有作为蛋白质动力学如何有助于分子识别的模型的巨大潜力。我们以前提出了小鼠抗体不同的发色团，并与使用三脉冲光子回波峰移光谱，证明了免疫系统能够产生抗体具有广泛的灵活性。我们现在报告的两个抗体，5D 11和10A 6之间形成的复合物的表征，和发色团配体，他们逐渐认识到，8-甲氧基芘-1，3，6-三磺酸（MPTS）。Ab基因的序列表明它们是从一个共同的前体进化而来的。我们还使用了各种光谱方法来探测Ab-MPTS复合物的光物理和动力学，并发现它们彼此相似，但与先前表征的抗MPTS抗体不同。结构研究表明，这种差异可能是由于一种独特的结合模式，其中MPTS夹在PheH 98的侧链和TrpL 91的侧链之间，PheH 98通过T-堆积与发色团相互作用，TrpL 91通过平行堆积与发色团相互作用。T-堆叠相互作用似乎介导皮秒时间尺度上的弛豫，而平行堆叠似乎介导超快，飞秒时间尺度上的弛豫，这主导了响应。因此，抗MPTS抗体不仅证明了同时使用两种限制性堆叠模式进行分子识别，而且还提供了一个独特的机会来表征动力学如何有助于分子识别。这两种类型的堆积在蛋白质和蛋白质复合物中很常见，它们可能同样有助于动力学和分子识别。
For years, antibodies (Abs) have been used as a paradigm for understanding how protein structure contributes to molecular recognition. However, with the ability to evolve Abs that recognize specific chromophores, they also have great potential as models for how protein dynamics contribute to molecular recognition. We previously raised murine Abs to different chromophores and, with the use of three-pulse photon echo peak shift spectroscopy, demonstrated that the immune system is capable of producing Abs with widely varying flexibility. We now report the characterization of the complexes formed between two Abs, 5D11 and 10A6, and the chromophoric ligand that they were evolved to recognize, 8-methoxypyrene-1,3,6-trisulfonic acid (MPTS). The sequences of the Ab genes indicate that they evolved from a common precursor. We also used a variety of spectroscopic methods to probe the photophysics and dynamics of the Ab–MPTS complexes and found that they are similar to each other but distinct from previously characterized anti-MPTS Abs. Structural studies revealed that this difference likely results from a unique mode of binding in which MPTS is sandwiched between the side chain of PheH98, which interacts with the chromophore via T-stacking, and the side chain of TrpL91, which interacts with the chromophore via parallel stacking. The T-stacking interaction appears to mediate relaxation on the picosecond time scale, while the parallel stacking appears to mediate relaxation on an ultrafast, femtosecond time scale, which dominates the response. The anti-MPTS Abs thus not only demonstrate the simultaneous use of the two limiting modes of stacking for molecular recognition, but also provide a unique opportunity to characterize how dynamics might contribute to molecular recognition. Both types of stacking are common in proteins and protein complexes where they may similarly contribute to dynamics and molecular recognition.
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影响因子：
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DOI：
--
发表时间：
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期刊：
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