工程化 PP7 病毒衣壳作为肽展示平台。
Engineering the PP7 Virus Capsid as a Peptide Display Platform.
机构信息
National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center , 89 Convent Avenue , New York , New York 10027 , United States.
出版信息
ACS Nano. 2019 Apr 23;13(4):4443-4454. doi: 10.1021/acsnano.8b09683. Epub 2019 Mar 26.
Abstract
As self-assembling polyvalent nanoscale structures that can tolerate substantial genetic and chemical modification, virus-like particles are useful in a variety of fields. Here we describe the genetic modification and structural characterization of the Leviviridae PP7 capsid protein as a platform for the presentation of functional polypeptides. This particle was shown to tolerate the display of sequences from 1 kDa (a cell penetrating peptide) to 14 kDa (the Fc-binding double Z-domain) on its exterior surface as C-terminal genetic fusions to the coat protein. In addition, a dimeric construct allowed the presentation of exogenous loops between capsid monomers and the simultaneous presentation of two different peptides at different positions on the icosahedral structure. The PP7 particle is thereby significantly more tolerant of these types of polypeptide additions than Qβ and MS2, the other Leviviridae-derived VLPs in common use.
摘要
作为能够耐受大量遗传和化学修饰的自组装多价纳米结构，病毒样颗粒在多个领域都有应用。在这里，我们描述了 Leviviridae PP7 衣壳蛋白的遗传修饰和结构特征，将其作为展示功能多肽的平台。结果表明，该颗粒能够耐受在其外表面展示从 1kDa（穿膜肽）到 14kDa（Fc 结合双 Z 结构域）的序列，作为衣壳蛋白的 C 末端遗传融合。此外，二聚体构建体允许在衣壳单体之间展示外源环，并且能够在二十面体结构的不同位置同时展示两种不同的肽。与 Qβ和 MS2（另两种常用的 Leviviridae 衍生 VLPs）相比，PP7 颗粒对这些类型的多肽添加的耐受性显著提高。
相似文献
1
Engineering the PP7 Virus Capsid as a Peptide Display Platform.工程化 PP7 病毒衣壳作为肽展示平台。
ACS Nano. 2019 Apr 23;13(4):4443-4454. doi: 10.1021/acsnano.8b09683. Epub 2019 Mar 26.
2
Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7.在 RNA 噬菌体 PP7 的病毒样颗粒上免疫展示多样化的肽，包括广泛交叉型中和人乳头瘤病毒 L2 表位。
Vaccine. 2010 Jun 17;28(27):4384-93. doi: 10.1016/j.vaccine.2010.04.049. Epub 2010 Apr 29.
3
Cryo electron microscopy reconstructions of the Leviviridae unveil the densest icosahedral RNA packing possible.丝状噬菌体科的冷冻电子显微镜重建揭示了可能的最密集二十面体RNA包装。
J Mol Biol. 2006 Nov 3;363(4):858-65. doi: 10.1016/j.jmb.2006.08.053. Epub 2006 Aug 24.
4
Exploring the Landscape of the PP7 Virus-like Particle for Peptide Display.探索 PP7 病毒样颗粒在肽展示方面的应用前景。
ACS Nano. 2023 Sep 26;17(18):18470-18480. doi: 10.1021/acsnano.3c06178. Epub 2023 Sep 5.
5
Immunogenic display of diverse peptides on virus-like particles of RNA phage MS2.多种肽在RNA噬菌体MS2的病毒样颗粒上的免疫原性展示。
J Mol Biol. 2008 Jun 27;380(1):252-63. doi: 10.1016/j.jmb.2008.04.049. Epub 2008 Apr 27.
6
Thermal stability of RNA phage virus-like particles displaying foreign peptides.展示外源肽的 RNA 噬菌体病毒样颗粒的热稳定性。
J Nanobiotechnology. 2011 May 24;9:22. doi: 10.1186/1477-3155-9-22.
7
The True Story and Advantages of RNA Phage Capsids as Nanotools.RNA噬菌体衣壳作为纳米工具的真实故事及优势
Intervirology. 2016;59(2):74-110. doi: 10.1159/000449503. Epub 2016 Nov 10.
8
Location of the bacteriophage P22 coat protein C-terminus provides opportunities for the design of capsid-based materials.噬菌体 P22 外壳蛋白 C 末端的位置为基于衣壳的材料设计提供了机会。
Biomacromolecules. 2013 Sep 9;14(9):2989-95. doi: 10.1021/bm400796c. Epub 2013 Aug 27.
9
Adeno-associated virus type 2 VP2 capsid protein is nonessential and can tolerate large peptide insertions at its N terminus.2型腺相关病毒VP2衣壳蛋白是非必需的，并且在其N端能耐受大的肽插入。
J Virol. 2004 Jun;78(12):6595-609. doi: 10.1128/JVI.78.12.6595-6609.2004.
10
In situ structures of the genome and genome-delivery apparatus in a single-stranded RNA virus.单链RNA病毒中基因组及基因组传递装置的原位结构
Nature. 2017 Jan 5;541(7635):112-116. doi: 10.1038/nature20589. Epub 2016 Dec 19.
引用本文的文献
1
Overcoming air-water interface-induced artifacts in Cryo-EM with protein nanocrates.利用蛋白质纳米载体克服冷冻电镜中空气-水界面诱导的伪影。
bioRxiv. 2025 Aug 18:2025.08.18.667046. doi: 10.1101/2025.08.18.667046.
2
Genetically Encoded Coat Protein-Based Yeast Display Libraries of Cyclic Peptides.基于基因编码外壳蛋白的环肽酵母展示文库。
ACS Synth Biol. 2025 Aug 15;14(8):2987-2998. doi: 10.1021/acssynbio.4c00873. Epub 2025 Jul 13.
3
Biomimetic Nanoparticle Based Targeted mRNA Vaccine Delivery as a Novel Therapy for Glioblastoma Multiforme.基于仿生纳米颗粒的靶向mRNA疫苗递送作为多形性胶质母细胞瘤的一种新型疗法
AAPS PharmSciTech. 2025 Feb 21;26(3):68. doi: 10.1208/s12249-025-03065-z.
4
Substructure-Specific Antibodies Against Fentanyl Derivatives.针对芬太尼衍生物的亚结构特异性抗体。
ACS Nano. 2025 Jan 28;19(3):3714-3725. doi: 10.1021/acsnano.4c14369. Epub 2025 Jan 10.
5
Multi-species cryoEM calibration and workflow verification standard.多物种 cryoEM 校准和工作流程验证标准。
Acta Crystallogr F Struct Biol Commun. 2024 Nov 1;80(Pt 11):320-327. doi: 10.1107/S2053230X24010318. Epub 2024 Oct 31.
6
Carbohydrate-Lectin Interactions Reprogram Dendritic Cells to Promote Type 1 Anti-Tumor Immunity.碳水化合物-凝集素相互作用重塑树突状细胞以促进 1 型抗肿瘤免疫。
ACS Nano. 2024 Oct 1;18(39):26770-26783. doi: 10.1021/acsnano.4c07360. Epub 2024 Sep 16.
7
Multi-species cryoEM calibration and workflow verification standard.多物种冷冻电镜校准与工作流程验证标准。
bioRxiv. 2024 Aug 5:2024.08.05.606612. doi: 10.1101/2024.08.05.606612.
8
Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing.用于肽免疫聚焦的免疫正交蛋白纳米颗粒的异源初免-加强免疫方案
ACS Nano. 2024 Jul 23;18(31):20083-100. doi: 10.1021/acsnano.4c00949.
9
CryoCycle your grids: Plunge vitrifying and reusing clipped grids to advance cryoEM democratization.对你的网格进行冷冻循环：快速冷冻玻璃化并重复使用裁剪后的网格，以推动冷冻电镜技术的普及。
Res Sq. 2024 Jul 2:rs.3.rs-4415026. doi: 10.21203/rs.3.rs-4415026/v1.
10
Purification of Single-Stranded RNA Bacteriophages and Host Receptors for Structural Determination Using Cryo-Electron Microscopy.使用冷冻电镜对单链 RNA 噬菌体和宿主受体进行结构测定的纯化。
Methods Mol Biol. 2024;2793:185-204. doi: 10.1007/978-1-0716-3798-2_13.
本文引用的文献
1
New tools for automated high-resolution cryo-EM structure determination in RELION-3.用于 RELION-3 中自动化高分辨率冷冻电镜结构测定的新工具。
Elife. 2018 Nov 9;7:e42166. doi: 10.7554/eLife.42166.
2
Multifunctional Enzyme Packaging and Catalysis in the Qβ Protein Nanoparticle.多功能酶包装和 Qβ 蛋白纳米颗粒中的催化作用。
Biomacromolecules. 2018 Oct 8;19(10):3945-3957. doi: 10.1021/acs.biomac.8b00885. Epub 2018 Aug 30.
3
Interaction of Viral Capsid-Derived Virus-Like Particles (VLPs) with the Innate Immune System.病毒衣壳衍生的病毒样颗粒（VLPs）与天然免疫系统的相互作用
Vaccines (Basel). 2018 Jul 2;6(3):37. doi: 10.3390/vaccines6030037.
4
Structural basis for antibody recognition of the NANP repeats in circumsporozoite protein.抗体识别环子孢子蛋白中 NANP 重复序列的结构基础。
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10438-E10445. doi: 10.1073/pnas.1715812114. Epub 2017 Nov 14.
5
Major findings and recent advances in virus-like particle (VLP)-based vaccines.病毒样颗粒（VLP）疫苗的主要发现和最新进展。
Semin Immunol. 2017 Dec;34:123-132. doi: 10.1016/j.smim.2017.08.014. Epub 2017 Sep 5.
6
Sortase-Mediated Ligation as a Modular Approach for the Covalent Attachment of Proteins to the Exterior of the Bacteriophage P22 Virus-like Particle.分选酶介导的连接作为一种将蛋白质共价连接到噬菌体P22病毒样颗粒外部的模块化方法。
Bioconjug Chem. 2017 Aug 16;28(8):2114-2124. doi: 10.1021/acs.bioconjchem.7b00296. Epub 2017 Jun 30.
7
Establishment of MicroRNA delivery system by PP7 bacteriophage-like particles carrying cell-penetrating peptide.通过携带细胞穿透肽的PP7噬菌体样颗粒建立微小RNA递送系统。
J Biosci Bioeng. 2017 Aug;124(2):242-249. doi: 10.1016/j.jbiosc.2017.03.012. Epub 2017 Apr 22.
8
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy.MotionCor2：用于改进冷冻电子显微镜的束流诱导运动的各向异性校正
Nat Methods. 2017 Apr;14(4):331-332. doi: 10.1038/nmeth.4193. Epub 2017 Feb 27.
9
Display of single-chain variable fragments on bacteriophage MS2 virus-like particles.单链可变片段在噬菌体MS2病毒样颗粒上的展示。
J Nanobiotechnology. 2017 Feb 13;15(1):13. doi: 10.1186/s12951-016-0240-7.
10
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination.cryoSPARC：用于快速无监督低温电子显微镜结构测定的算法。
Nat Methods. 2017 Mar;14(3):290-296. doi: 10.1038/nmeth.4169. Epub 2017 Feb 6.
Zotero 插件