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4m18

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Crystal Structure of Surfactant Protein-D D325A/R343V mutant in complex with trimannose (Man-a1,2Man-a1,2Man)

Structural highlights

4m18 is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.203Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Goh BC, Rynkiewicz MJ, Cafarella TR, White MR, Hartshorn KL, Allen K, Crouch EC, Calin O, Seeberger PH, Schulten K, Seaton BA. Molecular mechanisms of inhibition of influenza by surfactant protein d revealed by large-scale molecular dynamics simulation. Biochemistry. 2013 Nov 26;52(47):8527-38. doi: 10.1021/bi4010683. Epub 2013 Nov, 13. PMID:24224757 doi:http://dx.doi.org/10.1021/bi4010683

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m18"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4m18]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M18 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=PRD_900111:2alpha-alpha-mannobiose'>PRD_900111</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]] 3.203&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=PRD_900111:2alpha-alpha-mannobiose'>PRD_900111</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=4m18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m18 OCA], [https://pdbe.org/4m18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m18 RCSB], [https://www.ebi.ac.uk/pdbsum/4m18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m18 ProSAT]</span></td></tr>
 </table>

4m18

From Proteopedia

Current revision

Crystal Structure of Surfactant Protein-D D325A/R343V mutant in complex with trimannose (Man-a1,2Man-a1,2Man)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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