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Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

ABSTRACT: SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions.

SUBMITTER: Zhang X

PROVIDER: S-EPMC10320017 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

Zhang Xixi X Li Zimu Z Zhang Yanjun Y Liu Yutong Y Wang Jingjing J Liu Banghui B Chen Qiuluan Q Wang Qian Q Fu Lutang L Wang Peiyi P Zhong Xiaolin X Jin Liang L Yan Qihong Q Chen Ling L He Jun J Zhao Jincun J Xiong Xiaoli X

Life science alliance 20230704 9

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacte ...[more]

PMID: 37402591

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Project description:The recent pandemic triggered numerous societal efforts aimed to control and limit the spread of SARS-CoV-2. One of these aspects is related on how the virion interacts with inanimate surfaces, which might be the source of secondary infection. Although recent works address the adsorption of the spike protein on surfaces, there is no information concerning the long-range interactions between spike and surfaces, experimented by the virion when is dispersed in the droplet before its possible adsorption. Some descriptors, namely the interaction potentials per single protein and global potentials, were calculated in this work. These descriptors, evaluated for the closed and open states of the spike protein, are correlated to the long-range noncovalent interactions between the SARS-CoV-2 spikes and polymeric surfaces. They are associated with the surface's affinity towards SARS-CoV-2 dispersed in respiratory droplets or water solutions. Molecular-Dynamics simulations were performed to model the surface of three synthetic polymeric materials: Polypropylene (PP), Polyethylene Terephthalate (PET), and Polylactic Acid (PLA), used in Molecular Mechanics simulations to define the above potentials. The descriptors show a similar trend for the three surfaces, highlighting a greater affinity towards the spikes of PP and PLA over PET. For closed and open structures, the long-range interactions with the surfaces decreased in the following order PP ∼ PLA > PET and PLA > PP > PET, respectively. Thus, PLA and PP interact with the virion quite distant from these surfaces to a greater extent concerning the PET surface, however, the differences among the considered surfaces were small. The global potentials show that the long-range interactions are weak compared to classic binding energy of covalent or ionic bonds. The proposed descriptors are useful most of all for a comparative study aimed at quickly preliminary screening of polymeric surfaces. The obtained results should be validated by more accurate method which will be subject of a subsequent work.

Dataset Information

Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

Publications

Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

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