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2fyl

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2fyl, 1 NMR models ()
Ligands:
Gene: LRPAP1, A2MRAP (Homo sapiens), LRP1 (Homo sapiens)
Related: 2fyj, 1lre
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Haddock model of the complex between double module of LRP, CR56, and first domain of receptor associated protein, RAP-d1.

Publication Abstract from PubMed

The low-density lipoprotein receptor-related protein (LRP) interacts with more than 30 ligands of different sizes and structures that can all be replaced by the receptor-associated protein (RAP). The double module of complement type repeats, CR56, of LRP binds many ligands including all three domains of RAP and alpha2-macroglobulin, which promotes the catabolism of the Abeta-peptide implicated in Alzheimer's disease. To understand the receptor-ligand cross-talk, the NMR structure of CR56 has been solved and ligand binding experiments with RAP domain 1 (RAPd1) have been performed. From chemical shift perturbations of both binding partners upon complex formation, a HADDOCK model of the complex between CR56 and RAPd1 has been obtained. The binding residues are similar to a common binding motif suggested from alpha2-macroglobulin binding studies and provide evidence for an understanding of their mutual cross-competition pattern. The present structural results convey a simultaneous description of both binding partners of an LRP-ligand complex and open a route to a broader understanding of the binding specificity of the LRP receptor, which may involve a general four-residue receptor-ligand recognition motif common to all LRP ligands. The present result may be beneficial in the design of antagonists of ligand binding to the LDL receptor family, and especially of drugs for treatment of Alzheimer's disease.

Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif., Jensen GA, Andersen OM, Bonvin AM, Bjerrum-Bohr I, Etzerodt M, Thogersen HC, O'Shea C, Poulsen FM, Kragelund BB, J Mol Biol. 2006 Sep 29;362(4):700-16. Epub 2006 Jul 15. PMID:16938309

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

Disease

[AMRP_HUMAN] Note=In complex with the alpha-2-MR or gp330, it may have some role in the pathogenesis of membrane glomerular nephritis.

Function

[AMRP_HUMAN] Interacts with LRP1/alpha-2-macroglobulin receptor and glycoprotein 330. [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]

About this Structure

2fyl is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

  • Jensen GA, Andersen OM, Bonvin AM, Bjerrum-Bohr I, Etzerodt M, Thogersen HC, O'Shea C, Poulsen FM, Kragelund BB. Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif. J Mol Biol. 2006 Sep 29;362(4):700-16. Epub 2006 Jul 15. PMID:16938309 doi:10.1016/j.jmb.2006.07.013
  1. 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
  2. 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
  3. 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
  4. 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
  5. May P, Herz J. LDL receptor-related proteins in neurodevelopment. Traffic. 2003 May;4(5):291-301. PMID:12713657
  6. 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
  7. 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
  8. 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
  9. 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
  10. May P, Herz J. LDL receptor-related proteins in neurodevelopment. Traffic. 2003 May;4(5):291-301. PMID:12713657

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