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DARPIns 通过表位/抗体互补性识别 G-四链体。

G-Quadruplex Recognition by DARPIns through Epitope/Paratope Analogy.

机构信息

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Università degli Studi di Palermo, Viale delle Scienze, 90128, Palermo, Italy.

Université de Lorraine and CNRS LPCT UMR 7019, 54000, Nancy, France.

出版信息

Chemistry. 2022 Oct 12;28(57):e202201824. doi: 10.1002/chem.202201824. Epub 2022 Aug 22.

DOI:10.1002/chem.202201824
PMID:35791808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9804223/
Abstract

We investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4 s specific sensors. To this end we carried out all-atom molecular dynamic simulations to unravel the interactions between specific nucleic acids, including human-telomeric (h-telo), Bcl-2, and c-Myc, with different peptides, forming a DARPin/G4 complex. By comparing the sequences of DARPin with that of a peptide known for its high affinity for c-Myc, we show that the recognition cannot be ascribed to sequence similarity but, instead, depends on the complementarity between the three-dimensional arrangement of the molecular fragments involved: the α-helix/loops domain of DARPin and the G4 backbone. Our results reveal that DARPins tertiary structure presents a charged hollow region in which G4 can be hosted, thus the more complementary the structural shapes, the more stable the interaction.

摘要

我们研究了导致 DARPins 肽特异性识别鸟嘌呤四链体 (G4) 的机制，这可能导致 G4 特异性传感器的设计。为此，我们进行了全原子分子动力学模拟，以揭示不同肽与特定核酸（包括人端粒 (h-telo)、Bcl-2 和 c-Myc）之间的相互作用，形成 DARPin/G4 复合物。通过比较 DARPin 的序列与已知对 c-Myc 具有高亲和力的肽的序列，我们表明，识别不能归因于序列相似性，而是取决于涉及的分子片段的三维排列之间的互补性：DARPin 的α-螺旋/环结构域和 G4 骨架。我们的结果表明，DARPins 的三级结构呈现出一个带电荷的中空区域，其中可以容纳 G4，因此结构形状的互补性越强，相互作用越稳定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/d861a8348b78/CHEM-28-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/7071c01b219f/CHEM-28-0-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/6bd76e443897/CHEM-28-0-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/546c9edc1a69/CHEM-28-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/f8f85d168f7b/CHEM-28-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/0417a549d420/CHEM-28-0-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/3d994353818d/CHEM-28-0-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/6177d1b4d03e/CHEM-28-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/cf5ffad5330b/CHEM-28-0-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/644a768c866e/CHEM-28-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/d861a8348b78/CHEM-28-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/7071c01b219f/CHEM-28-0-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/9f4071e85cf5/CHEM-28-0-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/6bd76e443897/CHEM-28-0-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/f8f85d168f7b/CHEM-28-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/0417a549d420/CHEM-28-0-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/3d994353818d/CHEM-28-0-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/6177d1b4d03e/CHEM-28-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/cf5ffad5330b/CHEM-28-0-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/644a768c866e/CHEM-28-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd4/9804223/d861a8348b78/CHEM-28-0-g004.jpg

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本文引用的文献

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