6s8v: Difference between revisions

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<StructureSection load='6s8v' size='340' side='right'caption='[[6s8v]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='6s8v' size='340' side='right'caption='[[6s8v]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6s8v]] is a 4 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=6S8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S8V FirstGlance]. <br>
<table><tr><td colspan='2'>[[6s8v]] is a 4 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=6S8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S8V FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.8&#8491;</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]), SLC3A2, MDU1 ([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=EDO:1,2-ETHANEDIOL'>EDO</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=6s8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s8v OCA], [http://pdbe.org/6s8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s8v RCSB], [http://www.ebi.ac.uk/pdbsum/6s8v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s8v 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=6s8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s8v OCA], [https://pdbe.org/6s8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s8v RCSB], [https://www.ebi.ac.uk/pdbsum/6s8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s8v ProSAT]</span></td></tr>
</table>
</table>
== 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/4F2_HUMAN 4F2_HUMAN]] Required for the function of light chain amino-acid transporters. Involved in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. Involved in guiding and targeting of LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, is also involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. When associated with SLC7A5 or SLC7A8, involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Together with ICAM1, regulates the transport activity LAT2 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with SLC7A5, plays an important role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier.<ref>PMID:11557028</ref> <ref>PMID:9829974</ref> <ref>PMID:9751058</ref> <ref>PMID:9878049</ref> <ref>PMID:10903140</ref> <ref>PMID:11311135</ref> <ref>PMID:11389679</ref> <ref>PMID:11564694</ref> <ref>PMID:11742812</ref> <ref>PMID:12117417</ref> <ref>PMID:12225859</ref> <ref>PMID:14603368</ref> <ref>PMID:12716892</ref> <ref>PMID:15980244</ref> <ref>PMID:15769744</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 6s8v" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 6s8v" style="background-color:#fffaf0;"></div>
==See Also==
*[[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: Large Structures]]
[[Category: Large Structures]]
[[Category: Deuschle, F C]]
[[Category: Deuschle F-C]]
[[Category: Schiefner, A]]
[[Category: Schiefner A]]
[[Category: Skerra, A]]
[[Category: Skerra A]]
[[Category: Amino acid transport]]
[[Category: Anticalin]]
[[Category: Cd98hc]]
[[Category: Interaction with integrin beta subunit]]
[[Category: Lcn2]]
[[Category: Lipocalin]]
[[Category: Lipocalin-based binding protein]]
[[Category: Presentation of cd98 light chain]]
[[Category: Protein binding]]
[[Category: Single-pass type ii membrane protein]]

Latest revision as of 11:19, 17 October 2024

Structure of the high affinity Anticalin P3D11 in complex with the human CD98 heavy chain ectodomainStructure of the high affinity Anticalin P3D11 in complex with the human CD98 heavy chain ectodomain

Structural highlights

6s8v is a 4 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 1.8Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Enhanced amino acid supply and dysregulated integrin signaling constitute two hallmarks of cancer and are pivotal for metastatic transformation of cells. In line with its function at the crossroads of both processes, overexpression of CD98hc is clinically observed in various cancer malignancies, thus rendering it a promising tumor target. Methods: We describe the development of Anticalin proteins based on the lipocalin 2 (Lcn2) scaffold against the human CD98hc ectodomain (hCD98hcED) using directed evolution and protein design. X-ray structural analysis was performed to identify the epitope recognized by the lead Anticalin candidate. The Anticalin - with a tuned plasma half-life using PASylation((R)) technology - was labeled with (89)Zr and investigated by positron emission tomography (PET) of CD98-positive tumor xenograft mice. Results: The Anticalin P3D11 binds CD98hc with picomolar affinity and recognizes a protruding loop structure surrounded by several glycosylation sites within the solvent exposed membrane-distal part of the hCD98hcED. In vitro studies revealed specific binding activity of the Anticalin towards various CD98hc-expressing human tumor cell lines, suggesting broader applicability in cancer research. PET/CT imaging of mice bearing human prostate carcinoma xenografts using the optimized and (89)Zr-labeled Anticalin demonstrated strong and specific tracer accumulation (8.6 +/- 1.1 %ID/g) as well as a favorable tumor-to-blood ratio of 11.8. Conclusion: Our findings provide a first proof of concept to exploit CD98hc for non-invasive biomedical imaging. The novel Anticalin-based alphahCD98hc radiopharmaceutical constitutes a promising tool for preclinical and, potentially, clinical applications in oncology.

Development of a high affinity Anticalin((R)) directed against human CD98hc for theranostic applications.,Deuschle FC, Morath V, Schiefner A, Brandt C, Ballke S, Reder S, Steiger K, Schwaiger M, Weber W, Skerra A Theranostics. 2020 Jan 12;10(5):2172-2187. doi: 10.7150/thno.38968. eCollection, 2020. PMID:32089738[1]

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

See Also

References

  1. ↑ Deuschle FC, Morath V, Schiefner A, Brandt C, Ballke S, Reder S, Steiger K, Schwaiger M, Weber W, Skerra A. Development of a high affinity Anticalin((R)) directed against human CD98hc for theranostic applications. Theranostics. 2020 Jan 12;10(5):2172-2187. doi: 10.7150/thno.38968. eCollection, 2020. PMID:32089738 doi:http://dx.doi.org/10.7150/thno.38968

6s8v, resolution 1.80Å

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