3kq4

From Proteopedia

(Difference between revisions)

Current revision

Structure of Intrinsic Factor-Cobalamin bound to its receptor Cubilin

Structural highlights

3kq4 is a 6 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 3.3Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IF_HUMAN Defects in GIF are the cause of hereditary intrinsic factor deficiency (IFD) [MIM:261000; also known as congenital pernicious anemia. IFD is an autosomal recessive disorder characterized by megaloblastic anemia.^[1]

Function

IF_HUMAN Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Cobalamin (Cbl, vitamin B(12)) is a bacterial organic compound and an essential coenzyme in mammals, which take it up from the diet. This occurs by the combined action of the gastric intrinsic factor (IF) and the ileal endocytic cubam receptor formed by the 460-kilodalton (kDa) protein cubilin and the 45-kDa transmembrane protein amnionless. Loss of function of any of these proteins ultimately leads to Cbl deficiency in man. Here we present the crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution. The structure provides insight into how several CUB (for 'complement C1r/C1s, Uegf, Bmp1') domains collectively function as modular ligand-binding regions, and how two distant CUB domains embrace the Cbl molecule by binding the two IF domains in a Ca(2+)-dependent manner. This dual-point model provides a probable explanation of how Cbl indirectly induces ligand-receptor coupling. Finally, the comparison of Ca(2+)-binding CUB domains and the low-density lipoprotein (LDL) receptor-type A modules suggests that the electrostatic pairing of a basic ligand arginine/lysine residue with Ca(2+)-coordinating acidic aspartates/glutamates is a common theme of Ca(2+)-dependent ligand-receptor interactions.

Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes.,Andersen CB, Madsen M, Storm T, Moestrup SK, Andersen GR Nature. 2010 Mar 18;464(7287):445-8. PMID:20237569^[2]

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

References

↑ Tanner SM, Li Z, Perko JD, Oner C, Cetin M, Altay C, Yurtsever Z, David KL, Faivre L, Ismail EA, Grasbeck R, de la Chapelle A. Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4130-3. Epub 2005 Feb 28. PMID:15738392 doi:0500517102
↑ Andersen CB, Madsen M, Storm T, Moestrup SK, Andersen GR. Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. Nature. 2010 Mar 18;464(7287):445-8. PMID:20237569 doi:10.1038/nature08874

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3kq4"

@@ Line 1: / Line 1: @@
 ==Structure of Intrinsic Factor-Cobalamin bound to its receptor Cubilin==
-<StructureSection load='3kq4' size='340' side='right' caption='[[3kq4]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+<StructureSection load='3kq4' size='340' side='right'caption='[[3kq4]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3kq4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KQ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KQ4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3kq4]] 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=3KQ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KQ4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 3.3&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2pmw|2pmw]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GIF, IFMH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CUBN, IFCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3kq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kq4 OCA], [https://pdbe.org/3kq4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kq4 RCSB], [https://www.ebi.ac.uk/pdbsum/3kq4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kq4 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=3kq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kq4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kq4 RCSB], [http://www.ebi.ac.uk/pdbsum/3kq4 PDBsum]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/IF_HUMAN IF_HUMAN]] Defects in GIF are the cause of hereditary intrinsic factor deficiency (IFD) [MIM:[http://omim.org/entry/261000 261000]]; also known as congenital pernicious anemia. IFD is an autosomal recessive disorder characterized by megaloblastic anemia.<ref>PMID:15738392</ref>  [[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>
+[https://www.uniprot.org/uniprot/IF_HUMAN IF_HUMAN] Defects in GIF are the cause of hereditary intrinsic factor deficiency (IFD) [MIM:[https://omim.org/entry/261000 261000]; also known as congenital pernicious anemia. IFD is an autosomal recessive disorder characterized by megaloblastic anemia.<ref>PMID:15738392</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/IF_HUMAN IF_HUMAN]] Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis. [[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>
+[https://www.uniprot.org/uniprot/IF_HUMAN IF_HUMAN] Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/3kq4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/3kq4_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kq4 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 30: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3kq4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 35: / Line 36: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Andersen, C B.F]]
+[[Category: Large Structures]]
-[[Category: Andersen, G R]]
+[[Category: Andersen CBF]]
-[[Category: Madsen, M]]
+[[Category: Andersen GR]]
-[[Category: Moestrup, S K]]
+[[Category: Madsen M]]
-[[Category: Cholesterol metabolism]]
+[[Category: Moestrup SK]]
-[[Category: Cobalamin]]
-[[Category: Cobalt]]
-[[Category: Cobalt transport]]
-[[Category: Disease mutation]]
-[[Category: Disulfide bond]]
-[[Category: Egf-like domain]]
-[[Category: Endocytosis]]
-[[Category: Endosome]]
-[[Category: Glycoprotein]]
-[[Category: Lipid metabolism]]
-[[Category: Lysosome]]
-[[Category: Membrane]]
-[[Category: Protein transport]]
-[[Category: Protein-protein complex]]
-[[Category: Receptor]]
-[[Category: Secreted]]
-[[Category: Steroid metabolism]]
-[[Category: Transport]]
-[[Category: Transport protein]]

3kq4

From Proteopedia

Current revision

Structure of Intrinsic Factor-Cobalamin bound to its receptor Cubilin

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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