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==Crystal structure of Mumps virus hemagglutinin-neuraminidase==
==Crystal structure of Mumps virus hemagglutinin-neuraminidase==
<StructureSection load='5b2c' size='340' side='right' caption='[[5b2c]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
<StructureSection load='5b2c' size='340' side='right'caption='[[5b2c]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5b2c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B2C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B2C FirstGlance]. <br>
<table><tr><td colspan='2'>[[5b2c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mumps_orthorubulavirus Mumps orthorubulavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B2C FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.238&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5b2d|5b2d]]</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] </span></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=5b2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b2c OCA], [https://pdbe.org/5b2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b2c RCSB], [https://www.ebi.ac.uk/pdbsum/5b2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b2c ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5b2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b2c OCA], [http://pdbe.org/5b2c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b2c RCSB], [http://www.ebi.ac.uk/pdbsum/5b2c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b2c ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9WAF5_9MONO Q9WAF5_9MONO]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mumps virus (MuV) remains an important pathogen worldwide, causing epidemic parotitis, orchitis, meningitis, and encephalitis. Here we show that MuV preferentially uses a trisaccharide containing alpha2,3-linked sialic acid in unbranched sugar chains as a receptor. Crystal structures of the MuV attachment protein hemagglutinin-neuraminidase (MuV-HN) alone and in complex with the alpha2,3-sialylated trisaccharide revealed that in addition to the interaction between the MuV-HN active site residues and sialic acid, other residues, including an aromatic residue, stabilize the third sugar of the trisaccharide. The importance of the aromatic residue and the third sugar in the MuV-HN-receptor interaction was confirmed by computational energy calculations, isothermal titration calorimetry studies, and glycan-binding assays. Furthermore, MuV-HN was found to bind more efficiently to unbranched alpha2,3-sialylated sugar chains compared with branched ones. Importantly, the strategically located aromatic residue is conserved among the HN proteins of sialic acid-using paramyxoviruses, and alanine substitution compromised their ability to support cell-cell fusion. These results suggest that not only the terminal sialic acid but also the adjacent sugar moiety contribute to receptor function for mumps and these paramyxoviruses. The distribution of structurally different sialylated glycans in tissues and organs may explain in part MuV's distinct tropism to glandular tissues and the central nervous system. In the crystal structure, the epitopes for neutralizing antibodies are located around the alpha-helices of MuV-HN that are not well conserved in amino acid sequences among different genotypes of MuV. This may explain the fact that MuV reinfection sometimes occurs.
Trisaccharide containing alpha2,3-linked sialic acid is a receptor for mumps virus.,Kubota M, Takeuchi K, Watanabe S, Ohno S, Matsuoka R, Kohda D, Nakakita SI, Hiramatsu H, Suzuki Y, Nakayama T, Terada T, Shimizu K, Shimizu N, Shiroishi M, Yanagi Y, Hashiguchi T Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11579-11584. Epub 2016 Sep 26. PMID:27671656<ref>PMID:27671656</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5b2c" style="background-color:#fffaf0;"></div>
==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Exo-alpha-sialidase]]
[[Category: Large Structures]]
[[Category: Hashiguchi, T]]
[[Category: Mumps orthorubulavirus]]
[[Category: Hiramatsu, H]]
[[Category: Hashiguchi T]]
[[Category: Kohda, D]]
[[Category: Hiramatsu H]]
[[Category: Kubota, M]]
[[Category: Kohda D]]
[[Category: Matsuoka, R]]
[[Category: Kubota M]]
[[Category: Nakayama, T]]
[[Category: Matsuoka R]]
[[Category: Ohno, S]]
[[Category: Nakayama T]]
[[Category: Shimizu, K]]
[[Category: Ohno S]]
[[Category: Shimizu, N]]
[[Category: Shimizu K]]
[[Category: Suzuki, Y]]
[[Category: Shimizu N]]
[[Category: Takeuchi, K]]
[[Category: Suzuki Y]]
[[Category: Terada, T]]
[[Category: Takeuchi K]]
[[Category: Watanabe, S]]
[[Category: Terada T]]
[[Category: Yanagi, Y]]
[[Category: Watanabe S]]
[[Category: Beta-propeller]]
[[Category: Yanagi Y]]
[[Category: Glycoprotein]]
[[Category: Receptor binding]]
[[Category: Viral protein]]

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