9LH2
Crystal structure of SARS-CoV-2 spike receptor-binding domain (Delta) in complex with pH-dependent nanobody MNb-11.
Summary for 9LH2
| Entry DOI | 10.2210/pdb9lh2/pdb |
| Descriptor | Spike protein S1, MNb-11, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | complex, antiviral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) More |
| Total number of polymer chains | 4 |
| Total formula weight | 79981.22 |
| Authors | Zhang, X.D.,Lu, G.W. (deposition date: 2025-01-11, release date: 2026-01-14, Last modification date: 2026-03-11) |
| Primary citation | Zhang, X.,Chen, Z.,Lin, S.,Yang, F.,Guo, L.,Yang, J.,Wang, L.,Yuan, X.,Xu, P.,He, B.,Cao, Y.,Li, J.,Zhao, Q.,Li, J.,Yang, L.,Wang, W.,Wang, Z.,Yang, J.,Yang, J.,Shen, G.,Wei, X.,Lu, G. Modification of a SARS-CoV-2 spike-RBD targeting nanobody for pH-dependent binding and its chromatographic engineering for purification of WT and variant S-RBDs with mild elution conditions. Int.J.Biol.Macromol., 338:149749-149749, 2026 Cited by PubMed Abstract: For vaccine development against SARS-CoV-2, the spike (S) or spike receptor-binding domain (S-RBD) serves as the major antigen. Enhancing the efficiency and streamlining the process for S/S-RBD purification thus hold considerable practical significance. Here, we identify a basic and evolutionarily conserved region within S-RBD and select a nanobody targeting the region for structural-guided modifications. Histidine substitutions are introduced in the nanobody to enable pH-dependent binding to S-RBD. Two candidates, MNb-11 and MNb-14, are found to readily bind to S-RBD at pH 7.5 but lose the binding capacity below pH 5.0. During the chromatographic-purification trials, resins immobilized with MNb-11 or MNb-14 could purify both wild-type and variant S/S-RBD proteins in one step to a high level of purity and homogeneity. In addition, both modified nanobodies show superior stability across multiple binding-elution cycles. Taken together, our study presents a one-step affinity-chromatographic method for purifying the S/S-RBD protein, which should aid in vaccine development and production against SARS-CoV-2. PubMed: 41421699DOI: 10.1016/j.ijbiomac.2025.149749 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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