4m17: Difference between revisions
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==Crystal Structure of Surfactant Protein-D D325A/R343V mutant== | |||
<StructureSection load='4m17' size='340' side='right' caption='[[4m17]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4m17]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M17 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M17 FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m18|4m18]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">COLEC7, PSPD, SFTP4, SFTPD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4m17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m17 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m17 RCSB], [http://www.ebi.ac.uk/pdbsum/4m17 PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/SFTPD_HUMAN SFTPD_HUMAN]] Contributes to the lung's defense against inhaled microorganisms. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties. | [[http://www.uniprot.org/uniprot/SFTPD_HUMAN SFTPD_HUMAN]] Contributes to the lung's defense against inhaled microorganisms. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Surfactant protein D (SP-D), a mammalian C-type lectin, is the primary innate inhibitor of influenza A virus (IAV) in the lung. Interactions of SP-D with highly branched viral N-linked glycans on hemagglutinin (HA), an abundant IAV envelope protein and critical virulence factor, promote viral aggregation and neutralization through as yet unknown molecular mechanisms. Two truncated human SP-D forms, wild-type (WT) and double mutant D325A+R343V, representing neck and carbohydrate recognition domains are compared in this study. Whereas both WT and D325A+R343V bind to isolated glycosylated HA, WT does not inhibit IAV in neutralization assays; in contrast, D325A+R343V neutralization compares well with that of full-length native SP-D. To elucidate the mechanism for these biochemical observations, we have determined crystal structures of D325A+R343V in the presence and absence of a viral nonamannoside (Man9). On the basis of the D325A+R343V-Man9 structure and other crystallographic data, models of complexes between HA and WT or D325A+R343V were produced and subjected to molecular dynamics. Simulations reveal that whereas WT and D325A+R343V both block the sialic acid receptor site of HA, the D325A+R343V complex is more stable, with stronger binding caused by additional hydrogen bonds and hydrophobic interactions with HA residues. Furthermore, the blocking mechanism of HA differs for WT and D325A+R343V because of alternate glycan binding modes. The combined results suggest a mechanism through which the mode of SP-D-HA interaction could significantly influence viral aggregation and neutralization. These studies provide the first atomic-level molecular view of an innate host defense lectin inhibiting its viral glycoprotein target. | |||
Molecular mechanisms of inhibition of influenza by surfactant protein d revealed by large-scale molecular dynamics simulation.,Goh BC, Rynkiewicz MJ, Cafarella TR, White MR, Hartshorn KL, Allen K, Crouch EC, Calin O, Seeberger PH, Schulten K, Seaton BA Biochemistry. 2013 Nov 26;52(47):8527-38. doi: 10.1021/bi4010683. Epub 2013 Nov, 13. PMID:24224757<ref>PMID:24224757</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Allen, K | [[Category: Allen, K]] | ||
[[Category: Cafarella, T R | [[Category: Cafarella, T R]] | ||
[[Category: Calin, O | [[Category: Calin, O]] | ||
[[Category: Crouch, E C | [[Category: Crouch, E C]] | ||
[[Category: Goh, B C | [[Category: Goh, B C]] | ||
[[Category: Hartshorn, K L | [[Category: Hartshorn, K L]] | ||
[[Category: Rynkiewicz, M J | [[Category: Rynkiewicz, M J]] | ||
[[Category: Schulten, K | [[Category: Schulten, K]] | ||
[[Category: Seaton, B A | [[Category: Seaton, B A]] | ||
[[Category: Seeberger, P H | [[Category: Seeberger, P H]] | ||
[[Category: White, M R | [[Category: White, M R]] | ||
[[Category: Carbohydrate recognition domain]] | [[Category: Carbohydrate recognition domain]] | ||
[[Category: Lectin]] | [[Category: Lectin]] | ||
[[Category: Sugar binding protein]] | [[Category: Sugar binding protein]] | ||
[[Category: Surfactant protein]] | [[Category: Surfactant protein]] | ||