Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
Jun Lan,Jiwan Ge,Jinfang Yu,Sisi Shan,Huan Zhou,Shilong Fan,Qi Zhang,Xuanling Shi,Qisheng Wang,Linqi Zhang,Xinquan Wang +10 more
TLDR
High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.Abstract:
A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1–3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies. High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS-CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.read more
Citations
More filters
Posted ContentDOI
Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2
Shihui Sun,Hongjing Gu,Lei Cao,Qi Chen,Guan Yang,Ruiting Li,Hang Fan,Qing Ye,Yong-Qiang Deng,Xiaopeng Song,Yini Qi,Min Li,Jun Lan,Rui Feng,Lei Wang,Yifei Zhang,Chao Zhou,Lingna Zhao,Yuehong Chen,Meng Shen,Yujun Cui,Xiao Yang,Xinquan Wang,Hui Wang,Xiangxi Wang,Cheng-Feng Qin +25 more
TL;DR: A mouse adapted SARS-CoV-2 strain that harbored three amino acid substitutions in the RBD of S protein showed 100% mortality in aged, male BALB/c mice is generated and the molecular mechanism for the rapid adaption and evolution of Sars-Cov-2 in mice is unveiled.
Journal ArticleDOI
Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.
Linling He,Xiaohe Lin,Ying Wang,Ciril Abraham,Cindy Sou,Timothy Ngo,Yi Zhang,Ian A. Wilson,Jiang Zhu +8 more
TL;DR: In this article, the authors combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2, which provided an effective tool to combat the COVID-19 pandemic.
Journal ArticleDOI
Molecular diversity of coronavirus host cell entry receptors.
TL;DR: The latest advances in the field of coronavirus receptors are discussed, emphasizing on the molecular and evolutionary processes that underlie coronav virus receptor usage and host range expansion.
Journal ArticleDOI
Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern.
TL;DR: The L452R mutant, associated with the SARS-CoV-2 California VoC (B.1.427/B.429-California), has evolved to enhance ACE2 binding, while simultaneously disrupting C1 and C2 NAb classes, representing an excellent therapeutic option for treatment of Sars-Cov-2 WT and VoC strains.
Posted ContentDOI
An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity
Chihiro Motozono,Mako Toyoda,Jiri Zahradnik,Terumasa Ikeda,Akatsuki Saito,Toong Seng Tan,Isaac Ngare,Hesham Nasser,Izumi Kimura,Keiya Uriu,Yusuke Kosugi,Shiho Torii,Akiko Yonekawa,Nobuyuki Shimono,Yoji Nagasaki,Rumi Minami,Takashi Toya,Noritaka Sekiya,Takasuke Fukuhara,Yoshiharu Matsuura,Gideon Schreiber,So Nakagawa,Takamasa Ueno,Kei Sato +23 more
TL;DR: In this paper, two recently emerging mutants in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F, can escape from the HLA-24-restricted cellular immunity.
References
More filters
Journal ArticleDOI
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
Journal ArticleDOI
A Novel Coronavirus from Patients with Pneumonia in China, 2019.
Na Zhu,Dingyu Zhang,Wenling Wang,Xingwang Li,Bo Yang,Jingdong Song,Xiang Zhao,Baoying Huang,Weifeng Shi,Roujian Lu,Peihua Niu,Faxian Zhan,Xuejun Ma,Dayan Wang,Wenbo Xu,Wenbo Xu,Guizhen Wu,George F. Gao,Wenjie Tan +18 more
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Journal ArticleDOI
Phaser crystallographic software
Airlie J. McCoy,Ralf W. Grosse-Kunstleve,Paul D. Adams,Martyn Winn,Laurent C. Storoni,Randy J. Read +5 more
TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Related Papers (5)
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more