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| | ==Crystal structure of ligand-binding repeat CR7 from LRP== | | ==Crystal structure of ligand-binding repeat CR7 from LRP== |
| - | <StructureSection load='1j8e' size='340' side='right' caption='[[1j8e]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='1j8e' size='340' side='right'caption='[[1j8e]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1j8e]] is a 1 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=1J8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J8E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1j8e]] is a 1 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=1J8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J8E FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d2l|1d2l]], [[1cr8|1cr8]], [[1ajj|1ajj]]</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></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j8e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j8e RCSB], [http://www.ebi.ac.uk/pdbsum/1j8e PDBsum]</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=1j8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j8e OCA], [https://pdbe.org/1j8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j8e RCSB], [https://www.ebi.ac.uk/pdbsum/1j8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j8e ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LRP1_HUMAN LRP1_HUMAN] Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission.<ref>PMID:1702392</ref> <ref>PMID:1618748</ref> <ref>PMID:11907044</ref> <ref>PMID:12888553</ref> <ref>PMID:12713657</ref> Functions as a receptor for Pseudomonas aeruginosa exotoxin A.<ref>PMID:1702392</ref> <ref>PMID:1618748</ref> <ref>PMID:11907044</ref> <ref>PMID:12888553</ref> <ref>PMID:12713657</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j8/1j8e_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j8/1j8e_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> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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=1j8e ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1j8e" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Dolmer, K.]] | + | [[Category: Large Structures]] |
| - | [[Category: Gettins, P G.W.]] | + | [[Category: Dolmer K]] |
| - | [[Category: Huang, W.]] | + | [[Category: Gettins PGW]] |
| - | [[Category: Simonovic, M.]] | + | [[Category: Huang W]] |
| - | [[Category: Strickland, D K.]] | + | [[Category: Simonovic M]] |
| - | [[Category: Volz, K.]] | + | [[Category: Strickland DK]] |
| - | [[Category: Calcium binding]]
| + | [[Category: Volz K]] |
| - | [[Category: Complement-like repeat]]
| + | |
| - | [[Category: Ligand binding]]
| + | |
| - | [[Category: Lrp receptor]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
LRP1_HUMAN Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission.[1] [2] [3] [4] [5] Functions as a receptor for Pseudomonas aeruginosa exotoxin A.[6] [7] [8] [9] [10]
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
We have determined the X-ray crystal structure to 1.8 A resolution of the Ca(2+) complex of complement-like repeat 7 (CR7) from the low-density lipoprotein receptor-related protein (LRP) and characterized its calcium binding properties at pH 7.4 and 5. CR7 occurs in a region of the LRP that binds to the receptor-associated protein, RAP, and other protein ligands in a Ca(2+)-dependent manner. The calcium coordination is identical to that found in LB5 and consists of carboxyls from three conserved aspartates and one conserved glutamate, and the backbone carbonyls of a tryptophan and another aspartate. The overall fold of CR7 is similar to those of CR3 and CR8 from the LRP and LB5 from the LDL receptor, though the low degree of sequence homology of residues not involved in calcium coordination or in disulfide formation results in a distinct pattern of surface residues for each domain, including CR7. The thermodynamic parameters for Ca(2+) binding at both extracellular and endosomal pHs were determined by isothermal titration calorimetry for CR7 and for related complement-like repeats CR3, CR8, and LB5. Although the drop in pH resulted in a reduction in calcium affinity in each case, the changes were very variable in magnitude, being as low as a 2-fold reduction for CR3. This suggests that a pH-dependent change in calcium affinity alone cannot be responsible for the release of bound protein ligands from the LRP at the pH prevailing in the endosome, which in turn requires one or more other pH-dependent effects for regulating protein ligand release.
Calcium coordination and pH dependence of the calcium affinity of ligand-binding repeat CR7 from the LRP. Comparison with related domains from the LRP and the LDL receptor.,Simonovic M, Dolmer K, Huang W, Strickland DK, Volz K, Gettins PG Biochemistry. 2001 Dec 18;40(50):15127-34. PMID:11735395[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kristensen T, Moestrup SK, Gliemann J, Bendtsen L, Sand O, Sottrup-Jensen L. Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor. FEBS Lett. 1990 Dec 10;276(1-2):151-5. PMID:1702392
- ↑ Kounnas MZ, Morris RE, Thompson MR, FitzGerald DJ, Strickland DK, Saelinger CB. The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A. J Biol Chem. 1992 Jun 25;267(18):12420-3. PMID:1618748
- ↑ May P, Reddy YK, Herz J. Proteolytic processing of low density lipoprotein receptor-related protein mediates regulated release of its intracellular domain. J Biol Chem. 2002 May 24;277(21):18736-43. Epub 2002 Mar 20. PMID:11907044 doi:10.1074/jbc.M201979200
- ↑ Kinoshita A, Shah T, Tangredi MM, Strickland DK, Hyman BT. The intracellular domain of the low density lipoprotein receptor-related protein modulates transactivation mediated by amyloid precursor protein and Fe65. J Biol Chem. 2003 Oct 17;278(42):41182-8. Epub 2003 Jul 29. PMID:12888553 doi:10.1074/jbc.M306403200
- ↑ May P, Herz J. LDL receptor-related proteins in neurodevelopment. Traffic. 2003 May;4(5):291-301. PMID:12713657
- ↑ Kristensen T, Moestrup SK, Gliemann J, Bendtsen L, Sand O, Sottrup-Jensen L. Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor. FEBS Lett. 1990 Dec 10;276(1-2):151-5. PMID:1702392
- ↑ Kounnas MZ, Morris RE, Thompson MR, FitzGerald DJ, Strickland DK, Saelinger CB. The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A. J Biol Chem. 1992 Jun 25;267(18):12420-3. PMID:1618748
- ↑ May P, Reddy YK, Herz J. Proteolytic processing of low density lipoprotein receptor-related protein mediates regulated release of its intracellular domain. J Biol Chem. 2002 May 24;277(21):18736-43. Epub 2002 Mar 20. PMID:11907044 doi:10.1074/jbc.M201979200
- ↑ Kinoshita A, Shah T, Tangredi MM, Strickland DK, Hyman BT. The intracellular domain of the low density lipoprotein receptor-related protein modulates transactivation mediated by amyloid precursor protein and Fe65. J Biol Chem. 2003 Oct 17;278(42):41182-8. Epub 2003 Jul 29. PMID:12888553 doi:10.1074/jbc.M306403200
- ↑ May P, Herz J. LDL receptor-related proteins in neurodevelopment. Traffic. 2003 May;4(5):291-301. PMID:12713657
- ↑ Simonovic M, Dolmer K, Huang W, Strickland DK, Volz K, Gettins PG. Calcium coordination and pH dependence of the calcium affinity of ligand-binding repeat CR7 from the LRP. Comparison with related domains from the LRP and the LDL receptor. Biochemistry. 2001 Dec 18;40(50):15127-34. PMID:11735395
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