8w3p: Difference between revisions
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==Crystal structure of prefusion-stabilized RSV F protein UFCR3-D(1TD0)== | |||
<StructureSection load='8w3p' size='340' side='right'caption='[[8w3p]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8w3p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus_A2 Human respiratory syncytial virus A2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8W3P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8W3P FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8w3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8w3p OCA], [https://pdbe.org/8w3p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8w3p RCSB], [https://www.ebi.ac.uk/pdbsum/8w3p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8w3p ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F(2)-F(1) linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F structures and one hMPV-F structure), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identify three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites O and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induce robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development. | |||
Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus.,Lee YZ, Han J, Zhang YN, Ward G, Braz Gomes K, Auclair S, Stanfield RL, He L, Wilson IA, Zhu J Nat Commun. 2024 Nov 16;15(1):9939. doi: 10.1038/s41467-024-54287-x. PMID:39550381<ref>PMID:39550381</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8w3p" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Wilson | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Human respiratory syncytial virus A2]] | |||
[[Category: Large Structures]] | |||
[[Category: Lee YZ]] | |||
[[Category: Stanfield RL]] | |||
[[Category: Wilson IA]] | |||
[[Category: Zhu J]] | |||
Latest revision as of 09:12, 15 January 2025
Crystal structure of prefusion-stabilized RSV F protein UFCR3-D(1TD0)Crystal structure of prefusion-stabilized RSV F protein UFCR3-D(1TD0)
Structural highlights
Publication Abstract from PubMedRespiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F(2)-F(1) linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F structures and one hMPV-F structure), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identify three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites O and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induce robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development. Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus.,Lee YZ, Han J, Zhang YN, Ward G, Braz Gomes K, Auclair S, Stanfield RL, He L, Wilson IA, Zhu J Nat Commun. 2024 Nov 16;15(1):9939. doi: 10.1038/s41467-024-54287-x. PMID:39550381[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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