Yuhe R. Yang

Affiliated Eye Hospital of Wenzhou Medical College

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Andrew B. Ward

Scripps Institution of Oceanography

Dongsheng Liu

Tsinghua University

Hao Lin

University of Electronic Science and Technology of China

Hao Yan

Arizona State University

Yan Liu

Liaoning University of Technology

Yang Yang

State Key Laboratory of Oncogene and Related Genes

Minghui Liu

China Pharmaceutical University

Bini Zhou

Tsinghua University

Yuanchen Dong

Institute of Chemistry

Yunyun Xu

State Key Laboratory of Oncogene and Related Genes

Cooperative Institutions

Tsinghua University

Chinese Academy of Sciences

University of Electronic Science and Technology of China

Chinese Academy of Medical Sciences & Peking Union Medical College

Scripps Research Institute

Shanghai Jiao Tong University

University of Chinese Academy of Sciences

International AIDS Vaccine Initiative

Peking University

Sun Yat-sen University

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Human germinal centres engage memory and naive B cells after influenza vaccination

Nature (2020)

Jackson S. Turner Julian Q. Zhou Julianna Han Aaron J. Schmitz Amena A. Rizk

Memory B cell

Original antigenic sin

10.1038/s41586-020-2711-0

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Citations (255)

A Biostablel‐DNA Hydrogel with Improved Stability for Biomedical Applications

Angewandte Chemie (2022)

Bo Yang Bini Zhou Cuifeng Li Xiaowei Li Ziwei Shi

Abstract DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self‐assembly of a novel l ‐DNA hydrogel, which inherited the extraordinary physical properties of a d ‐DNA hydrogel. With the mirror‐isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the l ‐DNA hydrogel has been verified both in vitro and in vivo. Hence, this l ‐DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell‐culture matrix and implanted bio‐scaffold for long‐term biomedical applications.

Biocompatibility

Thixotropy

10.1002/ange.202202520

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Citations (16)

Mapping protein-protein interactions by solvent exposed amides experiment

KH Sze DH Lin X Liu Yuhe R. Yang X Guan

Source

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A Survey for Predicting ATP Binding Residues of Proteins Using Machine Learning Methods

Current Medicinal Chemistry (2021)

Yuhe R. Yang Jia-Shu Wang Shi-Shi Yuan Menglu Liu Wei Su

Abstract: Protein-ligand interactions are necessary for majority protein functions. Adenosine- 5’-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is costineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

Adenosine triphosphate

10.2174/0929867328666210910125802

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Influence of Tetra(ethylene glycol) (EG₄) Substitution at the Loop Region on the Intramolecular DNA i-Motif

Macromolecules (2012)

Yuhe R. Yang Yawei Sun Yang Yang Yongzheng Xing Tao Zhang

In this research, we employed tetra(ethylene glycol) (EG4) to substitute bases at the loop region of the intramolecular DNA i-motif formed by (CCCTAA)3CCC, and systematically studied the influence of such nonbase components on the stability and conformation of the formed structures by circular dichroism (CD), UV–vis spectroscopy and gel electrophoresis. We found that with all loop bases substituted, the i-motif structure can still form. The stability of the i-motif generally got weaker with the increase of the substitution number. Substitution at different positions might lead to different topologies. The findings above demonstrate that bases at the loop region play an important role on the stability and topology of the intramolecular DNA i-motif.

Structural motif

Motif (music)

10.1021/ma300230q

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Risk assessment of 2024 cattle H5N1 using age-stratified serosurveillance data

medRxiv (Cold Spring Harbor Laboratory) (2024)

Lin‐Lei Chen Xiaojuan Zhang Kang Zhang Brian Pui-Chun Chan Jacqueline Kwan Yuk Yuen

ABSTRACT The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024. Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1) to general population. In the initial screening of 180 serum specimens encompassing all age groups, 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against 2024 cattle H5N1, with all collected from older adults aged ≥60 years old. Further screening showed that 5.0% (15/300) of adults aged ≥70 years old had detectable nAb titers against the 2024 cattle H5N1. All serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r=0.3311, 95% confidence interval 0.2264 to 0.4283; P<0.0001). The nAb titer against seasonal H1N1 virus was 3.9-fold higher for patients with detectable H5N1 nAb than those without (geometric mean titer: 108.5 [95% CI 56.3-209.1] vs 27.9 [95% CI 21.0-37.0], P=0.0039), but there was no statistically significant difference between H5N1 and H3N2 nAb titer. There was no difference in demographics, comorbidities and clinical frailty scores between individuals with detectable H5N1 nAb and those without. Our findings suggest that most individuals lack nAb response against 2024 cattle H5N1 and there is an urgency to develop and evaluate H5N1 vaccine or prophylactic monoclonal antibodies. Immune imprinting may be responsible for the cross neutralization between H5N1 and H1N1 among older adults.

Antibody titer

10.1101/2024.12.23.24319580

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Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Aleksandar Antanasijevic Leigh M. Sewall Christopher A. Cottrell Diane G. Carnathan Luis Jiménez

In Brief Herein, we evaluated the immunogenicity of several BG505 SOSIP-based HIV Env immunogens in the rhesus macaque animal model using a combination of serology and biophysical approaches. We applied electron cryo-microscopy for high-resolution mapping of elicited polyclonal antibody responses, which provided detailed insights into the binding modes of the most common classes of antibodies elicited by BG505 SOSIP immunogens as well as the critical differences in immunogenicity that can occur as a consequence of engineered stabilizing mutations and partial glycan occupancy at different sites. Summary Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic. Graphical abstract

Polyclonal antibodies

Epitope mapping

HIV vaccine

10.1101/2021.01.28.428677

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2D Enzyme Cascade Network with Efficient Substrate Channeling by Swinging Arms

ChemBioChem (2017)

Yuhe R. Yang Jinglin Fu Shaun Wootten Xiaodong Qi Minghui Liu

In living cells, compartmentalized or membrane-associated enzymes are often assembled into large networks to cooperatively catalyze cascade reaction pathways essential for cellular metabolism. Here, we report the assembly of an artificial 2D enzyme network of two cascade enzymes-glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH)-on a wireframe DNA origami template. Swinging arms were used to facilitate the transport of the redox intermediate of NAD+ /NADH between enzyme pairs on the array. The assemblies of 2D enzyme networks were characterized by gel electrophoresis and visualized by atomic force microscopy (AFM). The spatial arrangements of multiple enzyme pairs were optimized to facilitate efficient substrate channeling by exploiting the programmability of DNA origami to manipulate the key parameters of swinging arm length and stoichiometry. Compared with a single enzyme pair, the 2D organized enzyme systems exhibited higher reaction efficiency due to the promoted transfer of intermediates within the network.

DNA origami

10.1002/cbic.201700613

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Citations (35)

Distinct Binding Modes of Inter-Spike Cross-Linking Suggest a Supplementary Mechanism for SARS-CoV-2 Antibody Neutralization

Xuanyu Nan Yujie Li Rui Zhang Ruoke Wang Nonghua Lv

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron subvariants drastically amplifies transmissibility, infectivity, and immune escape, mainly due to their resistance to most neutralizing antibodies. Thus, exploring the mechanisms underlying antibody evasion is crucial. Although the full-length native form of antibody, immunoglobulin G (IgG), offers valuable insights into the neutralization, structural investigations primarily focus on the fragment of antigen-binding (Fab). Here, we employ single-particle cryo-electron microscopy (cryo-EM) to characterize a W328-6H2 antibody, in its native IgG form complexed with severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 wild-type (WT) and Omicron variant BA.1 spike protein (S). Three high-resolution structures reveal that the full-length IgG forms a centered head-to-head dimer of trimer when bound fully stoichiometrically with both SARS and WT S, while adopting a distinct offset configuration with Omicron BA.1 S. Combined with functional assays, our results suggest that, beyond the binding affinity between the RBD epitope and Fab, the higher-order architectures of S trimer and full-length IgG play an additional role in neutralization, elucidate a potential molecular basis of Omicron immune escape, and expand our understanding on antibody evasion mechanisms.

spike protein

10.1101/2024.11.07.622402

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Prediction of N7-methylguanosine sites in human RNA based on optimal sequence features

Genomics (2020)

Yuhe R. Yang Chi Ma Jia-Shu Wang Hui Yang Hui Ding

Sequence (biology)

10.1016/j.ygeno.2020.07.035

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Citations (27)