View source for 6vjo


==Human parainfluenza virus type 3 fusion glycoprotein N-terminal heptad repeat domain+alpha/beta-VI==
<StructureSection load='6vjo' size='340' side='right'caption='[[6vjo]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vjo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_respirovirus_3 Human respirovirus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VJO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VJO 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=B3E:(3S)-3-AMINOHEXANEDIOIC+ACID'>B3E</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=XCP:(1S,2S)-2-AMINOCYCLOPENTANECARBOXYLIC+ACID'>XCP</scene>, <scene name='pdbligand=XPC:(3S,4R)-4-AMINOPYRROLIDINE-3-CARBOXYLIC+ACID'>XPC</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=6vjo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vjo OCA], [https://pdbe.org/6vjo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vjo RCSB], [https://www.ebi.ac.uk/pdbsum/6vjo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vjo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FUS_PI3H4 FUS_PI3H4] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (F protein) probably interacts with HN at the virion surface. Upon HN binding to its cellular receptor, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between cell and virion membranes. Later in infection, F proteins expressed at the plasma membrane of infected cells could mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The lower respiratory tract infections affecting children worldwide are in large part caused by the parainfluenza viruses (HPIVs), particularly HPIV3, along with human metapneumovirus and respiratory syncytial virus, enveloped negative-strand RNA viruses. There are no vaccines for these important human pathogens, and existing treatments have limited or no efficacy. Infection by HPIV is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. A viral fusion protein (F), once activated in proximity to a target cell, undergoes a series of conformational changes that first extend the trimer subunits to allow insertion of the hydrophobic domains into the target cell membrane and then refold the trimer into a stable postfusion state, driving the merger of the viral and host cell membranes. Lipopeptides derived from the C-terminal heptad repeat (HRC) domain of HPIV3 F inhibit infection by interfering with the structural transitions of the trimeric F assembly. Clinical application of this strategy, however, requires improving the in vivo stability of antiviral peptides. We show that the HRC peptide backbone can be modified via partial replacement of alpha-amino acid residues with beta-amino acid residues to generate alpha/beta-peptides that retain antiviral activity but are poor protease substrates. Relative to a conventional alpha-lipopeptide, our best alpha/beta-lipopeptide exhibits improved persistence in vivo and improved anti-HPIV3 antiviral activity in animals.

Engineering Protease-Resistant Peptides to Inhibit Human Parainfluenza Viral Respiratory Infection.,Outlaw VK, Cheloha RW, Jurgens EM, Bovier FT, Zhu Y, Kreitler DF, Harder O, Niewiesk S, Porotto M, Gellman SH, Moscona A J Am Chem Soc. 2021 Apr 21;143(15):5958-5966. doi: 10.1021/jacs.1c01565. Epub , 2021 Apr 7. PMID:33825470<ref>PMID:33825470</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vjo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Human respirovirus 3]]
[[Category: Large Structures]]
[[Category: Gellman SH]]
[[Category: Kreitler DF]]
[[Category: Outlaw VK]]