| 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 used NMR methods to determine the structure of the calcium complex of complement-like repeat 3 (CR3) from the low density lipoprotein receptor-related protein (LRP) and to examine its specific interaction with the receptor binding domain of human alpha(2)-macroglobulin. CR3 is one of eight related repeats that constitute a major ligand binding region of LRP. The structure is very similar in overall fold to homologous complement-like repeat CR8 from LRP and complement-like repeats LB1, LB2, and LB5 from the low density lipoprotein receptor and contains a short two-strand antiparallel beta-sheet, a one turn alpha-helix, and a high affinity calcium site with coordination from four carboxyls and two backbone carbonyls. The surface electrostatics and topography are, however, quite distinct from each of these other repeats. Two-dimensional (1)H,(15)N-heteronuclear single quantum coherence spectra provide evidence for a specific, though relatively weak (K(d) approximately 140 microM), interaction between CR3 and human alpha2-macroglobulin receptor binding domain that involves a contiguous patch of surface residues in the central region of CR3. This specific interaction is consistent with a mode of LRP binding to ligands that uses contributions from more than one domain to generate a wide array of different binding sites, each with overall high affinity.
NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin.,Dolmer K, Huang W, Gettins PG J Biol Chem. 2000 Feb 4;275(5):3264-9. PMID:10652313[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
- ↑ Dolmer K, Huang W, Gettins PG. NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin. J Biol Chem. 2000 Feb 4;275(5):3264-9. PMID:10652313
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