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| | <StructureSection load='6usc' size='340' side='right'caption='[[6usc]], [[Resolution|resolution]] 1.59Å' scene=''> | | <StructureSection load='6usc' size='340' side='right'caption='[[6usc]], [[Resolution|resolution]] 1.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6usc]] is a 2 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=6USC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6USC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6usc]] is a 2 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=6USC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6USC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KO2:PROP-2-EN-1-YL+D-GLYCERO-ALPHA-D-TALO-OCT-2-ULOPYRANOSIDONIC+ACID'>KO2</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]] 1.59Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITLN1, INTL, ITLN, LFR, UNQ640/PRO1270 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KO2:PROP-2-EN-1-YL+D-GLYCERO-ALPHA-D-TALO-OCT-2-ULOPYRANOSIDONIC+ACID'>KO2</scene></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=6usc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6usc OCA], [http://pdbe.org/6usc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6usc RCSB], [http://www.ebi.ac.uk/pdbsum/6usc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6usc ProSAT]</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=6usc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6usc OCA], [https://pdbe.org/6usc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6usc RCSB], [https://www.ebi.ac.uk/pdbsum/6usc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6usc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ITLN1_HUMAN ITLN1_HUMAN]] Has no effect on basal glucose uptake but enhances insulin-stimulated glucose uptake in adipocytes. Increases AKT phosphorylation in the absence and presence of insulin. May play a role in the defense system against microorganisms. May specifically recognize carbohydrate chains of pathogens and bacterial components containing galactofuranosyl residues, in a calcium-dependent manner. May be involved in iron metabolism.<ref>PMID:11313366</ref> <ref>PMID:16531507</ref> | + | [https://www.uniprot.org/uniprot/ITLN1_HUMAN ITLN1_HUMAN] Has no effect on basal glucose uptake but enhances insulin-stimulated glucose uptake in adipocytes. Increases AKT phosphorylation in the absence and presence of insulin. May play a role in the defense system against microorganisms. May specifically recognize carbohydrate chains of pathogens and bacterial components containing galactofuranosyl residues, in a calcium-dependent manner. May be involved in iron metabolism.<ref>PMID:11313366</ref> <ref>PMID:16531507</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Isabella, C R]] | + | [[Category: Isabella CR]] |
| - | [[Category: Kiessling, L L]] | + | [[Category: Kiessling LL]] |
| - | [[Category: Kosma, P]] | + | [[Category: Kosma P]] |
| - | [[Category: Raines, R T]] | + | [[Category: Raines RT]] |
| - | [[Category: Windsor, I W]] | + | [[Category: Windsor IW]] |
| - | [[Category: Ko]]
| + | |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Microbial recognition]]
| + | |
| - | [[Category: Sugar binding protein]]
| + | |
| Structural highlights
Function
ITLN1_HUMAN Has no effect on basal glucose uptake but enhances insulin-stimulated glucose uptake in adipocytes. Increases AKT phosphorylation in the absence and presence of insulin. May play a role in the defense system against microorganisms. May specifically recognize carbohydrate chains of pathogens and bacterial components containing galactofuranosyl residues, in a calcium-dependent manner. May be involved in iron metabolism.[1] [2]
Publication Abstract from PubMed
Recognition of distinct glycans is central to biology, and lectins mediate this function. Lectin glycan preferences are usually centered on specific monosaccharides. In contrast, human intelectin-1 (hItln-1, also known as Omentin-1) is a soluble lectin that binds a range of microbial sugars, including beta-D-galactofuranose (beta-Galf), D-glycerol 1-phosphate, D-glycero-D-talo-oct-2-ulosonic acid (KO), and 3-deoxy-D-manno-oct-2-ulosonic acid (KDO). Though these saccharides differ dramatically in structure, they share a common feature-an exocyclic vicinal diol. How and whether such a small fragment is sufficient for recognition was unclear. We tested several glycans with this epitope and found that L-glycero-alpha-D-manno-heptose and D-glycero-alpha-D-manno-heptose possess the critical diol motif yet bind weakly. To better understand hItln-1 recognition, we determined the structure of the hItln-1.KO complex using X-ray crystallography, and our 1.59-A resolution structure enabled unambiguous assignment of the bound KO conformation. This carbohydrate conformation was present in >97% of the KDO/KO structures in the Protein Data Bank. Bioinformatic analysis revealed that KO and KDO adopt a common conformation, while heptoses prefer different conformers. The preferred conformers of KO and KDO favor hItln-1 engagement, but those of the heptoses do not. Natural bond orbital (NBO) calculations suggest these observed conformations, including the side chain orientations, are stabilized by not only steric but also stereoelectronic effects. Thus, our data highlight a role for stereoelectronic effects in dictating the specificity of glycan recognition by proteins. Finally, our finding that hItln-1 avoids binding prevalent glycans with a terminal 1,2 diol (e.g., NeuAc, and L-glycero-alpha-D-manno-heptose) suggests the lectin has evolved to recognize distinct bacterial species.
Stereoelectronic effects impact glycan recognition.,McMahon CM, Isabella CR, Windsor IW, Kosma P, Raines RT, Kiessling LL J Am Chem Soc. 2020 Jan 13. doi: 10.1021/jacs.9b11699. PMID:31930911[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tsuji S, Uehori J, Matsumoto M, Suzuki Y, Matsuhisa A, Toyoshima K, Seya T. Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall. J Biol Chem. 2001 Jun 29;276(26):23456-63. Epub 2001 Apr 19. PMID:11313366 doi:http://dx.doi.org/10.1074/jbc.M103162200
- ↑ Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, Gong DW. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab. 2006 Jun;290(6):E1253-61. Epub 2006 Mar 10. PMID:16531507 doi:http://dx.doi.org/00572.2004
- ↑ McMahon CM, Isabella CR, Windsor IW, Kosma P, Raines RT, Kiessling LL. Stereoelectronic effects impact glycan recognition. J Am Chem Soc. 2020 Jan 13. doi: 10.1021/jacs.9b11699. PMID:31930911 doi:http://dx.doi.org/10.1021/jacs.9b11699
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