5W23
Crystal Structure of RSV F in complex with 5C4 Fab
Summary for 5W23
| Entry DOI | 10.2210/pdb5w23/pdb |
| Descriptor | Fusion glycoprotein F0, 5C4 Fab heavy chain, 5C4 Fab light chain, ... (4 entities in total) |
| Functional Keywords | rsv, complex, fab, antibody, neutralizing antibody, viral protein-immune system complex, viral protein/immune system |
| Biological source | Human respiratory syncytial virus A More |
| Cellular location | Virion membrane; Single-pass type I membrane protein: P03420 |
| Total number of polymer chains | 9 |
| Total formula weight | 350086.04 |
| Authors | Battles, M.B.,McLellan, J.S. (deposition date: 2017-06-05, release date: 2017-12-06, Last modification date: 2024-11-13) |
| Primary citation | Tian, D.,Battles, M.B.,Moin, S.M.,Chen, M.,Modjarrad, K.,Kumar, A.,Kanekiyo, M.,Graepel, K.W.,Taher, N.M.,Hotard, A.L.,Moore, M.L.,Zhao, M.,Zheng, Z.Z.,Xia, N.S.,McLellan, J.S.,Graham, B.S. Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein. Nat Commun, 8:1877-1877, 2017 Cited by PubMed Abstract: A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different. Mutagenesis and virological studies demonstrate that RSV F residue 201 is largely responsible for the subtype specificity of 5C4. These results improve our understanding of subtype-specific immunity and the neutralization breadth requirements of next-generation antibodies, and thereby contribute to the design of broadly protective RSV vaccines. PubMed: 29187732DOI: 10.1038/s41467-017-01858-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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