8w3e: Difference between revisions
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==Crystal structure of prefusion-stabilized RSV F protein UFCR1== | |||
<StructureSection load='8w3e' size='340' side='right'caption='[[8w3e]], [[Resolution|resolution]] 2.26Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8w3e]] 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=8W3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8W3E 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]] 2.26Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=8w3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8w3e OCA], [https://pdbe.org/8w3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8w3e RCSB], [https://www.ebi.ac.uk/pdbsum/8w3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8w3e 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 8w3e" style="background-color:#fffaf0;"></div> | ||
[[Category: Stanfield | == 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]] | |||