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| | ==Structure of Anticalin N7E in complex with the three-domain fragment Fn7B8 of human oncofetal fibronectin== | | ==Structure of Anticalin N7E in complex with the three-domain fragment Fn7B8 of human oncofetal fibronectin== |
| - | <StructureSection load='5n47' size='340' side='right' caption='[[5n47]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='5n47' size='340' side='right'caption='[[5n47]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5n47]] is a 6 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=5N47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N47 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5n47]] is a 6 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=5N47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N47 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5n48|5n48]], [[4gh7|4gh7]]</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]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LCN2, HNL, NGAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FN1, FN ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5n47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n47 OCA], [https://pdbe.org/5n47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n47 RCSB], [https://www.ebi.ac.uk/pdbsum/5n47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n47 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=5n47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n47 OCA], [http://pdbe.org/5n47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n47 RCSB], [http://www.ebi.ac.uk/pdbsum/5n47 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n47 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN]] Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:[http://omim.org/entry/601894 601894]]; also known as familial glomerular nephritis with fibronectin deposits or fibronectin glomerulopathy. GFND is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life.<ref>PMID:18268355</ref> | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NGAL_HUMAN NGAL_HUMAN]] Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.<ref>PMID:12453413</ref> [[http://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN]] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref> Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref> | + | [https://www.uniprot.org/uniprot/NGAL_HUMAN NGAL_HUMAN] Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.<ref>PMID:12453413</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5n47" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5n47" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Fibronectin 3D structures|Fibronectin 3D structures]] |
| | + | *[[Neutrophil gelatinase-associated lipocalin|Neutrophil gelatinase-associated lipocalin]] |
| | + | *[[Siderocalin 3D structures|Siderocalin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Schiefner, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Skerra, A]] | + | [[Category: Schiefner A]] |
| - | [[Category: Anticalin]] | + | [[Category: Skerra A]] |
| - | [[Category: Ed-b]]
| + | |
| - | [[Category: Eiiib]]
| + | |
| - | [[Category: Extra-domain b]]
| + | |
| - | [[Category: Extracellular matrix]]
| + | |
| - | [[Category: Fn type iii domain]]
| + | |
| - | [[Category: Human fibronectin]]
| + | |
| - | [[Category: Lipocalin]]
| + | |
| - | [[Category: Lipocalin-based binding protein]]
| + | |
| - | [[Category: Oncofetal splice variant]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Function
NGAL_HUMAN Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.[1]
Publication Abstract from PubMed
We describe the comparative X-ray structural analysis of three Anticalin proteins directed against the extra-domain B (ED-B) of oncofetal fibronectin (Fn), a validated marker of tumor neoangiogenesis. The Anticalins were engineered from the human lipocalin 2 (Lcn2) scaffold via targeted randomization of the structurally variable loop region and selection by phage display, resulting in 15-19 exchanged residues. While the four reshaped loops exhibit diverse conformations (with shifts in Calpha positions up to 20.4 A), the beta-barrel core of the lipocalin remains strongly conserved, thus confirming the extraordinary robustness of this scaffold. All three Anticalins bind the cc' hairpin loop of ED-B, the most exposed motif in the context of its neighboring Fn domains, but reveal entirely different binding modes, with orientations differing by up to 180 degrees . Hence, each Anticalin recognizes its molecular target in an individual manner, in line with the distinct epitope specificities previously seen in binding experiments.
Anticalins Reveal High Plasticity in the Mode of Complex Formation with a Common Tumor Antigen.,Schiefner A, Gebauer M, Richter A, Skerra A Structure. 2018 Mar 5. pii: S0969-2126(18)30043-1. doi:, 10.1016/j.str.2018.02.003. PMID:29526433[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002 Nov;10(5):1045-56. PMID:12453413
- ↑ Schiefner A, Gebauer M, Richter A, Skerra A. Anticalins Reveal High Plasticity in the Mode of Complex Formation with a Common Tumor Antigen. Structure. 2018 Mar 5. pii: S0969-2126(18)30043-1. doi:, 10.1016/j.str.2018.02.003. PMID:29526433 doi:http://dx.doi.org/10.1016/j.str.2018.02.003
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