View source for 9qvu


==Crystal structure of human lung surfactant protein D trimeric fragment with bound synthetic HepI-(1,5)-KdoI ligand==
<StructureSection load='9qvu' size='340' side='right'caption='[[9qvu]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qvu]] is a 3 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=9QVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QVU 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]] 1.75&#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=GMH:L-GLYCERO-D-MANNO-HEPTOPYRANOSE'>GMH</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=9qvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qvu OCA], [https://pdbe.org/9qvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qvu RCSB], [https://www.ebi.ac.uk/pdbsum/9qvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qvu ProSAT]</span></td></tr>
</table>
== Function ==
[https://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.
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== Publication Abstract from PubMed ==
The innate immune protein human surfactant protein D (SP-D) recognises pathogens in the lungs via binding to carbohydrate surface structures. SP-D targets gram-negative bacterial lipopolysaccharide via calcium-dependent binding, preferentially to the inner core heptose (HepI). To further investigate this recognition, we have determined the high-resolution crystal structures of a trimeric recombinant fragment of human SP-D complexed with synthetic di- and trisaccharides, HepI-Kdo, HepIII-HepII-HepI, and HepII-HepI phosphorylated at either HepI or HepII, inner core lipopolysaccharide motifs common to many gram-negative bacteria. In contrast to acid-hydrolysed lipopolysaccharide used in several previous studies, these synthetic saccharides allow presentation of both the innermost Kdo in its natural pyranose form and heptose phosphorylation. The structures confirm the flexibility of SP-D to adopt alternative binding modes when the preferred epitope is not available, reveal a preference for recognition of the reducing terminal heptose (HepI) via the glyceryl group, indicate that a single Kdo attached to HepI does not have a significant role in ligand recognition, and provide evidence that heptose phosphorylation is a major determinant of recognition. The disaccharide with HepII O4' phosphorylation binds via the preferred HepI glyceryl-hydroxyls, while HepI O4' phosphorylation reveals HepII binding via the pyranose ring O3' and O4' hydroxyls, which would not be possible with the usual HepII O3' link to the outer core. The ability of HepI O4' phosphorylation to prevent preferred HepI recognition suggests a role for heptose phosphorylation in shielding the bacterial LPS inner core from immune recognition.

Phosphorylation of inner core heptose is a major determinant of bacterial surface lipopolysaccharide recognition by the innate immune protein hSP-D.,Williams HM, Watson A, Madsen J, Clark HW, Hood DW, Oscarson S, Greenhough TJ, Shrive AK J Biol Chem. 2026 Feb 20:111307. doi: 10.1016/j.jbc.2026.111307. PMID:41724382<ref>PMID:41724382</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qvu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Greenhough TJ]]
[[Category: Shrive AK]]
[[Category: Williams HM]]