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| - | [[Image:1cr8.gif|left|200px]]<br /> | |
| - | <applet load="1cr8" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1cr8" /> | |
| - | '''LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN COMPLEMENT REPEAT 8'''<br /> | |
| | | | |
| - | ==Overview== | + | ==LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN COMPLEMENT REPEAT 8== |
| - | The low density lipoprotein receptor-related protein is a member of the, low density lipoprotein receptor family and contains clusters of, cysteine-rich complement-like repeats of about 42 residues that are, present in all members of this family of receptors. These clusters are, thought to be the principal binding sites for protein ligands. We have, expressed one complement-like repeat, CR8, from the cluster in lipoprotein, receptor-related protein that binds certain proteinase, inhibitor-proteinase complexes and used three-dimensional NMR on the, 13C/15N-labeled protein to determine the structure in solution of the, calcium-bound form. The structure is very similar in overall fold to, repeat 5 from the low density lipoprotein receptor (LB5), with backbone, root mean square deviation of 1.5 A. The calcium-binding site also appears, to be homologous, with four carboxyl and two backbone carbonyl ligands., However, differences in primary structure are such that equivalent, surfaces that might represent the binding interfaces are very different, from one another, indicating that different domains will have very, different ligand specificities. | + | <StructureSection load='1cr8' size='340' side='right'caption='[[1cr8]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1cr8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CR8 FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cr8 OCA], [https://pdbe.org/1cr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cr8 RCSB], [https://www.ebi.ac.uk/pdbsum/1cr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cr8 ProSAT]</span></td></tr> |
| | + | </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 == |
| | + | [[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/cr/1cr8_consurf.spt"</scriptWhenChecked> |
| | + | <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/main_output.php?pdb_ID=1cr8 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The low density lipoprotein receptor-related protein is a member of the low density lipoprotein receptor family and contains clusters of cysteine-rich complement-like repeats of about 42 residues that are present in all members of this family of receptors. These clusters are thought to be the principal binding sites for protein ligands. We have expressed one complement-like repeat, CR8, from the cluster in lipoprotein receptor-related protein that binds certain proteinase inhibitor-proteinase complexes and used three-dimensional NMR on the 13C/15N-labeled protein to determine the structure in solution of the calcium-bound form. The structure is very similar in overall fold to repeat 5 from the low density lipoprotein receptor (LB5), with backbone root mean square deviation of 1.5 A. The calcium-binding site also appears to be homologous, with four carboxyl and two backbone carbonyl ligands. However, differences in primary structure are such that equivalent surfaces that might represent the binding interfaces are very different from one another, indicating that different domains will have very different ligand specificities. |
| | | | |
| - | ==Disease==
| + | NMR solution structure of complement-like repeat CR8 from the low density lipoprotein receptor-related protein.,Huang W, Dolmer K, Gettins PG J Biol Chem. 1999 May 14;274(20):14130-6. PMID:10318830<ref>PMID:10318830</ref> |
| - | Known diseases associated with this structure: Leigh syndrome, French-Canadian type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607544 607544]], Urolithiasis, 2,8-dihydroxyadenine OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102600 102600]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1CR8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CR8 OCA].
| + | </div> |
| - | | + | <div class="pdbe-citations 1cr8" style="background-color:#fffaf0;"></div> |
| - | ==Reference== | + | == References == |
| - | NMR solution structure of complement-like repeat CR8 from the low density lipoprotein receptor-related protein., Huang W, Dolmer K, Gettins PG, J Biol Chem. 1999 May 14;274(20):14130-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10318830 10318830]
| + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Dolmer, K.]] | + | [[Category: Dolmer K]] |
| - | [[Category: Gettins, P.G.W.]] | + | [[Category: Gettins PGW]] |
| - | [[Category: Huang, W.]] | + | [[Category: Huang W]] |
| - | [[Category: CA]]
| + | |
| - | [[Category: calcium binding]]
| + | |
| - | [[Category: ldlr]]
| + | |
| - | [[Category: ligand binding]]
| + | |
| - | [[Category: lrp]]
| + | |
| - | [[Category: receptor]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:24:39 2007''
| + | |
| 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
The low density lipoprotein receptor-related protein is a member of the low density lipoprotein receptor family and contains clusters of cysteine-rich complement-like repeats of about 42 residues that are present in all members of this family of receptors. These clusters are thought to be the principal binding sites for protein ligands. We have expressed one complement-like repeat, CR8, from the cluster in lipoprotein receptor-related protein that binds certain proteinase inhibitor-proteinase complexes and used three-dimensional NMR on the 13C/15N-labeled protein to determine the structure in solution of the calcium-bound form. The structure is very similar in overall fold to repeat 5 from the low density lipoprotein receptor (LB5), with backbone root mean square deviation of 1.5 A. The calcium-binding site also appears to be homologous, with four carboxyl and two backbone carbonyl ligands. However, differences in primary structure are such that equivalent surfaces that might represent the binding interfaces are very different from one another, indicating that different domains will have very different ligand specificities.
NMR solution structure of complement-like repeat CR8 from the low density lipoprotein receptor-related protein.,Huang W, Dolmer K, Gettins PG J Biol Chem. 1999 May 14;274(20):14130-6. PMID:10318830[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
- ↑ Huang W, Dolmer K, Gettins PG. NMR solution structure of complement-like repeat CR8 from the low density lipoprotein receptor-related protein. J Biol Chem. 1999 May 14;274(20):14130-6. PMID:10318830
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