Synthetic nanobody–SARS-CoV-2 receptor-binding domain structures identify distinct epitopes
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Abstract
The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demands unprecedented attention. We report four X-ray crystal structures of three synthetic nanobodies (sybodies) (Sb16, Sb45 and Sb68) bind to the receptor-binding domain (RBD) of SARS-CoV-2: binary complexes of Sb16–RBD and Sb45–RBD; a ternary complex of Sb45–RBD–Sb68; and Sb16 unliganded. Sb16 and Sb45 bind the RBD at the ACE2 interface, positioning their CDR2 and CDR3 loops diametrically. Sb16 reveals a large CDR2 shift when binding the RBD. Sb68 interacts peripherally at the ACE2 interface; steric clashes with glycans explain its mechanism of viral neutralization. Superposing these structures onto trimeric spike (S) protein models indicates these sybodies bind conformations of the mature S protein differently, which may aid therapeutic design.
One Sentence Summary
X-ray structures of synthetic nanobodies complexed with the receptor-binding domain of the spike protein of SARS-CoV-2 reveal details of CDR loop interactions in recognition of distinct epitopic sites.
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SciScore for 10.1101/2021.01.27.428466: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources Graded and increasing concentrations of SB16, SB45 and SB68 were injected over the RBD-immobilized surface at a flow rate of 30 μl/min with an association time of 120 s and dissociation time of 2000 s. SB45suggested: NoneSoftware and Algorithms Sentences Resources Subsequent refinements were carried out with PHENIX (44). PHENIXsuggested: (Phenix, RRID:SCR_014224)CDR loops were manually rebuilt by fitting to the electron density maps with Coot (45). Cootsuggested: (Coot, RRID:SCR_014222)Illustrations and calculations of superpositioned models were prepared in PyMOL (The PyMOL … SciScore for 10.1101/2021.01.27.428466: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources Graded and increasing concentrations of SB16, SB45 and SB68 were injected over the RBD-immobilized surface at a flow rate of 30 μl/min with an association time of 120 s and dissociation time of 2000 s. SB45suggested: NoneSoftware and Algorithms Sentences Resources Subsequent refinements were carried out with PHENIX (44). PHENIXsuggested: (Phenix, RRID:SCR_014224)CDR loops were manually rebuilt by fitting to the electron density maps with Coot (45). Cootsuggested: (Coot, RRID:SCR_014222)Illustrations and calculations of superpositioned models were prepared in PyMOL (The PyMOL Molecular Graphics System, Version 2.4.0 Schrodinger, LLC). PyMOLsuggested: (PyMOL, RRID:SCR_000305)Calculation of hinge relationships of domains was accomplished with HINGE (https://niaidsis.niaid.nih.gov/hinge.html), provided courtesy of Peter Sun, NIAID. HINGEsuggested: (Hinge, RRID:SCR_016135)Buried surface area (BSA) calculations were performed with PISA (https://www.ebi.ac.uk/pdbe/pisa/). PISAsuggested: (PISA, RRID:SCR_015749)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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