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2kny

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2kny, 20 NMR models ()
Ligands:
Gene: LRP1, A2MR, APR (Homo sapiens)


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Fusion construct of CR17 from LRP-1 and ApoE residues 130-149

Publication Abstract from PubMed

Clusters of complement-type ligand-binding repeats (CRs) in the low-density lipoprotein receptor (LDLR) family are thought to mediate the interactions with their various ligands. Apolipoprotein E (ApoE), a key ligand for cholesterol homeostasis, has been shown to interact with LDLR-related protein 1 (LRP) through these clusters. The segment comprising the receptor-binding portion of ApoE (residues 130-149) has been found to have a weak affinity for isolated CRs. We have fused this region of ApoE to a high-affinity CR from LRP (CR17) for structural elucidation of the complex. The interface reveals a motif that has previously been observed in CR domains with other binding partners, but with several novel features. Comparison to free CR17 reveals that very few structural changes result from this binding event, but significant changes in intrinsic dynamics are observed upon binding. NMR perturbation experiments suggest that this interface may be similar to several other ligand interactions with LDLRs.

Structure of the minimal interface between ApoE and LRP., Guttman M, Prieto JH, Handel TM, Domaille PJ, Komives EA, J Mol Biol. 2010 Apr 30;398(2):306-19. Epub 2010 Mar 19. PMID:20303980

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

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]

About this Structure

2kny is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

  • Guttman M, Prieto JH, Handel TM, Domaille PJ, Komives EA. Structure of the minimal interface between ApoE and LRP. J Mol Biol. 2010 Apr 30;398(2):306-19. Epub 2010 Mar 19. PMID:20303980 doi:10.1016/j.jmb.2010.03.022
  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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