杨雨荷 - 中国科学院国家纳米科学中心 -

个人简介

National Center for Nanoscience and Technology, Chinese Academy of Sciences 2017-2021 The Scripps Research Institute, La Jolla, CA, USA.Postdoctoral Research Associate; Advisor: Andrew B. Ward 2011-2016 The Biodesign Institute, Arizona State University, AZ, USA. Ph.D. in biochemistry; Advisor: Hao Yan 2007-2011 Tsinghua University, Beijing, P. R. China. B.S. in Chemistry, Advisor: Dongsheng Liu

研究领域

Methodology development: putting enzymes on DNA scaffold. In nature, the catalytic efficiency of multienzyme complexes highly depends on their spatial organization. The positions and orientations of the composite enzymes are often precisely controlled to facilitate substrate transport between them. Self-assembled DNA nanostructures hold great promise for organizing biomolecules at the nanoscale. Here, we present detailed protocols for exploiting DNA nanostructures as assembly scaffolds that organize the spatial arrangements of multienzyme cascades with control over their relative distance, compartmentalization and substrate diffusion paths. The protocol describes the preparation and purification of DNA-conjugated enzymes and cofactors, along with the assembly of these prepared complexes on DNA nanostructures. The architecture of assembled enzyme complexes is then readily characterized using a broad selection of techniques from routine gel electrophoresis to advanced single-molecule imaging. We also describe methods of purifying these nano-assemblies and testing them with functional assays based on either bulk or single-molecule fluorescence measurements. The entire assembly and characterization of a multienzyme complex can be completed within 1–2 weeks. An Artificial Swinging arm on DNA nanoscaffold. Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes1. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein–DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity. Gaining momentum by swinging arms. We assembled an artificial 2D enzyme network of two related dehydrogenase enzymes on a wireframe DNA origami template to facilitate swinging of the redox intermediate substrate to enhance enzyme cascade activity. The 2D organized enzyme system exhibited higher reaction efficiency than single enzyme pairs due to promoted transfer of intermediates within the network. CryoEM structure reveals detailed immune responses. HIV vaccine development has been A glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer-immunized rabbits. Our high-resolution cryo-electron microscopy (cryoEM) studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that even for the immunodominant glycan hole shared between BG505 and B41, the prospect of designing prime-boost immunogens remains difficult.

近期论文

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Effects of Univariate Stiffness and Degradation of DNA Hydrogels on the Transcriptomics of Neural Progenitor Cells. 2023. Journal of the American Chemical Society Bini Zhou, Bo Yang, Qian Liu, Lu Jin, Yu Shao, Taoyang Yuan, Ya-nan Zhang, Chao Wang, Ziwei Shi, Xin Li, Yufan Pan, Ning Qiao, Jiang-Fei Xu, Yuhe Renee Yang*, Yuanchen Dong, Lijin Xu, Songbai Gui*, and Dongsheng Liu* An Infectious Virus-like Particle Built on a Programmable Icosahedral DNA Framework. 2023. Angewandte Chemie 135 (4), e202214731 Y Xu, YR Yang, Q Shi, AB Ward, K Huang, X Chen, W Wang, Y Yang Cellular Ingestible DNA Nanostructures for Biomedical Applications. 2022. Advanced NanoBiomed Research, 2200119 R Xu, Y Li, C Zhu, D Liu*, YR Yang* Studies on the Synergistic Effect of Tandem Semi-Stable Complementary Domains on Sequence-Defined DNA Block Copolymers. 2022. Journal of the American Chemical Society Xin Li，Xiaobin Dai，Yufan Pan，Yawei Sun，Bo Yang，Kun Chen，You Wang，Jiang-Fei Xu ，Yuanchen Dong ，Yuhe Renee Yang*，Li-Tang Yan，Dongsheng Liu* A Biostable l-DNA Hydrogel with Improved Stability for Biomedical Applications. 2022.Angewandte Chemie. 61 (30), e202202520 Bo Yang, Bini Zhou, Cuifeng Li, Xiaowei Li, Ziwei Shi, Yuxin Li, Chenyou Zhu, Xin Li, Yi Hua, Yufan Pan, Jian He, Tianyang Cao, Prof. Yawei Sun, Prof. Wanli Liu, Min Ge, Prof. Yuhe R. Yang, Prof. Yuanchen Dong, Prof. Dongsheng Liu Influence of Tetra(ethylene glycol) (EG4) Substitution at the Loop Region on the Intramolecular DNA i-Motif.2012.Macromolecules 45:2643-2647. Yang Y, Sun Y, Yang Y, Xing Y, Zhang T, Wang Z, Yang Z, Liu D*. A DNA tweezer-actuated enzyme nanoreactor.2013.Nature communications 4:1-5.Liu M, Fu J, Hejesen C, Yang Y, Woodbury NW, Gothelf K, Liu Y, Yan H*. Directional regulation of enzyme pathways through the control of substrate channeling on a DNA origami scaffold.2016.Angewandte Chemie International Edition 55:7483-7486.Ke G, Liu M, Jiang S, Qi X, Yang YR, Wootten S, Zhang F, Zhu Z, Liu Y, Yang CJ*. Cuboid Vesicles Formed by Frame‐Guided Assembly on DNA Origami Scaffolds.2017.Angewandte Chemie International Edition 56:1586-1589.Dong Y, Yang YR, Zhang Y, Wang D, Wei X, Banerjee S, Liu Y, Yang Z, Yan H, Liu D*. The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization.2019.Cell reports 27:586-598. e6.Lei L, Yang YR, Tran K, Wang Y, Chiang C-I, Ozorowski G, Xiao Y, Ward AB, Wyatt RT, Li Y*. A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice.2020.Vaccines 2020, 8, 389.Thrane, S., Aves, K.-L., Uddbäck, I.E.M., Janitzek, C.M., Han, J., Yang, Y.R., Ward, A.B., Theander, T.G., Nielsen, M.A., Salanti, A., Thomsen, A.R., Christensen, J.P., Sander, A.F. Germinal centre-mediated diversification of human B cell response to influenza vaccination.2020.Nature 586: 127-131.Turner JS†, Zhou JQ†, Han J†, Schmitz AJ, Rizk A, Al-Soussi W, Lei, T, Amor M, McIntire KM, Meade P, Strohmeier S, Brent R, Richey S, Haile A, Yang YR, Klebert M, Suessen T, Teefey S, Presti R, Krammer F, Kleinstein SH, Ward AB, Ellebedy AH*. Exploring the speed limit of toehold exchange with a cartwheeling DNA acrobat.2018.Nature nanotechnology 13:723-729.Li J, Johnson-Buck A, Yang YR, Shih WM, Yan H, Walter NG*. DNA nanostructures as programmable biomolecular scaffolds.2015.Bioconjugate chemistry 26:1381-1395. Yang YR, Liu Y, Yan H*. Assembly of multienzyme complexes on DNA nanostructures.2016. Nature protocols 11:2243.Fu J, Yang YR, Dhakal S, Zhao Z, Liu M, Zhang T, Walter NG, Yan H*. 2D Enzyme Cascade Network with Efficient Substrate Channeling by Swinging Arms. 2018. ChemBioChem 19:212-216.Yang YR, Fu J, Wootten S, Qi X, Liu M, Yan H, Liu Y*. Autologous neutralizing antibody responses to an HIV envelope glycan hole are not easily broadened in rabbits.2020. Journal of Virology 94 (7), e01861-19.Yang YR†, McCoy LE†, van Gils MJ, Andrabi R, Turner HL, Yuan M, Cottrell CA, Ozorowski G, Voss J, Pauthner M, Polveroni TM, Messmer T, Wilson IA, Sanders RW, Burton DR, Ward AB*. Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm.2014,Nature nanotechnology 9:531. Fu J†, Yang YR†, Johnson-Buck A, Liu M, Liu Y, Walter NG, Woodbury NW, Yan H*.