7d30

Structure of sybody MR17-SR31 fusion in complex with the SARS-CoV-2 S Receptor Binding domain (RBD)

spinqualitylabelsall models 7d30, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7d30 is a 2 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 1PE, ACT, BMA, BU2, CD, FUC, GOL, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A key step to the SARS-CoV-2 infection is the attachment of its Spike receptor-binding domain (S RBD) to the host receptor ACE2. Considerable research has been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. Simple and effective strategies to increase potency are desirable for such studies when antibodies are only modestly effective. Here, we identify and characterize a high-affinity synthetic nanobody (sybody, SR31) as a fusion partner to improve the potency of RBM-antibodies. Crystallographic studies reveal that SR31 binds to RBD at a conserved and 'greasy' site distal to RBM. Although SR31 distorts RBD at the interface, it does not perturb the RBM conformation, hence displaying no neutralizing activities itself. However, fusing SR31 to two modestly neutralizing sybodies dramatically increases their affinity for RBD and neutralization activity against SARS-CoV-2 pseudovirus. Our work presents a tool protein and an efficient strategy to improve nanobody potency. A high-affinity RBD-targeting nanobody improves fusion partner's potency against SARS-CoV-2.,Yao H, Cai H, Li T, Zhou B, Qin W, Lavillette D, Li D PLoS Pathog. 2021 Mar 3;17(3):e1009328. doi: 10.1371/journal.ppat.1009328. , eCollection 2021 Mar. PMID:33657135 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Spike protein 3D structures

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