Dynamic Asymmetry Exposes 2019-nCoV Prefusion Spike
| Autor: | Susmita Roy, Raju Sarkar, Akhilesh Jaiswar |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Letter Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) media_common.quotation_subject Protein domain medicine.disease_cause Asymmetry Viral Proteins 03 medical and health sciences 0302 clinical medicine Protein Domains medicine General Materials Science Conformational energy Physical and Theoretical Chemistry 030304 developmental biology Coronavirus media_common Physics 0303 health sciences Spike Protein Molecular machine Spike Glycoprotein Coronavirus Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Physical Chemistry Letters |
| ISSN: | 1948-7185 |
| DOI: | 10.1021/acs.jpclett.0c01431 |
| Popis: | The novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a symmetry-information-loaded structure-based Hamiltonian is developed using recent Cryo-EM structural data to explore the complete conformational energy landscape of the full-length prefusion spike protein. The study finds the 2019-nCoV prefusion spike to adopt a unique strategy by undertaking a dynamic conformational asymmetry that results in two prevalent asymmetric structures of spike where one or two spike heads rotate up to provide better exposure to the host-cell receptor. A few unique interchain interactions are identified at the interface of closely associated N-terminal domain (NTD) and receptor binding domain (RBD) playing a crucial role in the thermodynamic stabilization of the up conformation of the RBD in the case of the 2019-nCoV spike. The interaction-level information decoded in this study may provide deep insight into developing effective therapeutic targets. |
| Databáze: | OpenAIRE |
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