6gje

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==Structure of the Amnionless(20-357)-Cubilin(36-135) complex==
==Structure of the Amnionless(20-357)-Cubilin(36-135) complex==
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<StructureSection load='6gje' size='340' side='right' caption='[[6gje]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='6gje' size='340' side='right'caption='[[6gje]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6gje]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GJE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6gje]] 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=6GJE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GJE FirstGlance]. <br>
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</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=6gje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gje OCA], [http://pdbe.org/6gje PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gje RCSB], [http://www.ebi.ac.uk/pdbsum/6gje PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gje ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6gje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gje OCA], [https://pdbe.org/6gje PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gje RCSB], [https://www.ebi.ac.uk/pdbsum/6gje PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gje ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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<div style="background-color:#fffaf0;">
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[[http://www.uniprot.org/uniprot/AMNLS_HUMAN AMNLS_HUMAN]] Graesbeck-Imerslund disease. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/CUBN_HUMAN CUBN_HUMAN]] Grasbeck-Imerslund disease. Defects in CUBN are a cause of recessive hereditary megaloblastic anemia 1 (RH-MGA1) [MIM:[http://omim.org/entry/261100 261100]]; also known as MGA1 Norwegian type or Imerslund-Grasbeck syndrome (I-GS). RH-MGA1 is due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected.<ref>PMID:10080186</ref> <ref>PMID:10887099</ref>
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== Publication Abstract from PubMed ==
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== Function ==
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The endocytic receptor cubam formed by the 460-kDa protein cubilin and the 45-kDa transmembrane protein amnionless (AMN), is essential for intestinal vitamin B12 (B12) uptake and for protein (e.g. albumin) reabsorption from the kidney filtrate. Loss of function of any of the two components ultimately leads to serious B12 deficiency and urinary protein loss in humans (Imerslund-Grasbeck's syndrome, IGS). Here, we present the crystal structure of AMN in complex with the amino-terminal region of cubilin, revealing a sophisticated assembly of three cubilin subunits combining into a single intertwined beta-helix domain that docks to a corresponding three-faced beta-helix domain in AMN. This beta-helix-beta-helix association thereby anchors three ligand-binding cubilin subunits to the transmembrane AMN. Electron microscopy of full-length cubam reveals a 700-800 A long tree-like structure with the potential of dimerization into an even larger complex. Furthermore, effects of known human mutations causing IGS are explained by the structural information.
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[[http://www.uniprot.org/uniprot/AMNLS_HUMAN AMNLS_HUMAN]] Necessary for efficient absorption of vitamin B12 (PubMed:12590260, PubMed:14576052). Required for normal CUBN-mediated protein transport in the kidney. May direct the production of trunk mesoderm during development by modulating a bone morphogenetic protein (BMP) signaling pathway in the underlying visceral endoderm (By similarity).[UniProtKB:Q99JB7]<ref>PMID:14576052</ref> <ref>PMID:12590260</ref> [[http://www.uniprot.org/uniprot/CUBN_HUMAN CUBN_HUMAN]] Cotransporter which plays a role in lipoprotein, vitamin and iron metabolism, by facilitating their uptake. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the GIF-cobalamin complex. The binding of all ligands requires calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. Interaction with LRP2 mediates its trafficking throughout vesicles and facilitates the uptake of specific ligands like GC, hemoglobin, ALB, TF and SCGB1A1. Interaction with AMN controls its trafficking to the plasma membrane and facilitates endocytosis of ligands. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface.<ref>PMID:9572993</ref> <ref>PMID:10371504</ref> <ref>PMID:11717447</ref> <ref>PMID:11606717</ref> <ref>PMID:14576052</ref>
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Structural assembly of the megadalton-sized receptor for intestinal vitamin B12 uptake and kidney protein reabsorption.,Larsen C, Etzerodt A, Madsen M, Skjodt K, Moestrup SK, Andersen CBF Nat Commun. 2018 Dec 6;9(1):5204. doi: 10.1038/s41467-018-07468-4. PMID:30523278<ref>PMID:30523278</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6gje" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Andersen, C B.F]]
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[[Category: Homo sapiens]]
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[[Category: Etzerodt, A]]
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[[Category: Large Structures]]
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[[Category: Larsen, C]]
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[[Category: Andersen CBF]]
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[[Category: Madsen, M]]
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[[Category: Etzerodt A]]
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[[Category: Moestrup, S K]]
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[[Category: Larsen C]]
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[[Category: Skjoedt, K]]
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[[Category: Madsen M]]
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[[Category: Amn]]
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[[Category: Moestrup SK]]
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[[Category: Amnionless]]
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[[Category: Skjoedt K]]
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[[Category: Cubilin]]
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[[Category: Cubn]]
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[[Category: Kidney]]
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[[Category: Protein transport]]
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[[Category: Proximal tubule]]
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[[Category: Reabsorption]]
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[[Category: Receptor]]
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[[Category: Vitamin b12]]
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Current revision

Structure of the Amnionless(20-357)-Cubilin(36-135) complex

PDB ID 6gje

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