View source for 7sem


==Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins==
<StructureSection load='7sem' size='340' side='right'caption='[[7sem]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sem]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_metapneumovirus Human metapneumovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SEM 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]] 2.2&#8491;</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=7sem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sem OCA], [https://pdbe.org/7sem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sem RCSB], [https://www.ebi.ac.uk/pdbsum/7sem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sem ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/H6X1Z0_9MONO H6X1Z0_9MONO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 degrees C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies.

Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins.,Hsieh CL, Rush SA, Palomo C, Chou CW, Pickens W, Mas V, McLellan JS Nat Commun. 2022 Mar 14;13(1):1299. doi: 10.1038/s41467-022-28931-3. PMID:35288548<ref>PMID:35288548</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7sem" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human metapneumovirus]]
[[Category: Large Structures]]
[[Category: Hsieh C-L]]
[[Category: McLellan JS]]
[[Category: Rush SA]]