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PDBsum entry 1ldl
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Binding protein PDB id
1ldl

 

 

 

 

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Contents
Protein chain
46 a.a. *
* Residue conservation analysis
PDB id:
1ldl
Name: Binding protein
Title: Three-dimensional structure of a cysteine-rich repeat from the low- density lipoprotein receptor
Structure: Low-density lipoprotein receptor. Chain: a. Fragment: ligand-binding domain, first repeat. Synonym: lb1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: human. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 10 models
Authors: N.L.Daly,M.J.Scanlon,P.A.Kroon,R.Smith
Key ref: N.L.Daly et al. (1995). Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor. Proc Natl Acad Sci U S A, 92, 6334-6338. PubMed id: 7603991 DOI: 10.1073/pnas.92.14.6334
Date:
20-Mar-95     Release date:   08-Mar-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01130  (LDLR_HUMAN) -  Low-density lipoprotein receptor from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		860 a.a.
46 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1073/pnas.92.14.6334 Proc Natl Acad Sci U S A 92:6334-6338 (1995)
PubMed id: 7603991  
 
 
Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor.
N.L.Daly, M.J.Scanlon, J.T.Djordjevic, P.A.Kroon, R.Smith.
 
  ABSTRACT  
 
The low-density lipoprotein (LDL) receptor plays a central role in mammalian cholesterol metabolism, clearing lipoproteins which bear apolipoproteins E and B-100 from plasma. Mutations in this molecule are associated with familial hypercholesterolemia, a condition which leads to an elevated plasma cholesterol concentration and accelerated atherosclerosis. The N-terminal segment of the LDL receptor contains a heptad of cysteine-rich repeats that bind the lipoproteins. Similar repeats are present in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. The first repeat of the human LDL receptor has been expressed in Escherichia coli as a glutathione S-transferase fusion protein, and the cleaved and purified receptor module has been shown to fold to a single, fully oxidized form that is recognized by the monoclonal antibody IgG-C7 in the presence of calcium ions. The three-dimensional structure of this module has been determined by two-dimensional NMR spectroscopy and shown to consist of a beta-hairpin structure, followed by a series of beta turns. Many of the side chains of the acidic residues, including the highly conserved Ser-Asp-Glu triad, are clustered on one face of the module. To our knowledge, this structure has not previously been described in any other protein and may represent a structural paradigm both for the other modules in the LDL receptor and for the homologous domains of several other proteins. Calcium ions had only minor effects on the CD spectrum and no effect on the 1H NMR spectrum of the repeat, suggesting that they induce no significant conformational change.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20089850 F.Pena, A.Jansens, G.van Zadelhoff, and I.Braakman (2010).
Calcium as a crucial cofactor for low density lipoprotein receptor folding in the endoplasmic reticulum.
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20303980 M.Guttman, J.H.Prieto, T.M.Handel, P.J.Domaille, and E.A.Komives (2010).
Structure of the minimal interface between ApoE and LRP.
  J Mol Biol, 398, 306-319.
PDB codes: 2knx 2kny
19899171 X.Arias-Moreno, S.Cuesta-Lopez, O.Millet, J.Sancho, and A.Velazquez-Campoy (2010).
Thermodynamics of protein-cation interaction: Ca(+2) and Mg(+2) binding to the fifth binding module of the LDL receptor.
  Proteins, 78, 950-961.  
19676115 D.Beglov, C.J.Lee, A.De Biasio, D.Kozakov, R.Brenke, S.Vajda, and N.Beglova (2009).
Structural insights into recognition of beta2-glycoprotein I by the lipoprotein receptors.
  Proteins, 77, 940-949.  
19459784 R.H.Palmer, E.Vernersson, C.Grabbe, and B.Hallberg (2009).
Anaplastic lymphoma kinase: signalling in development and disease.
  Biochem J, 420, 345-361.  
19329437 T.Yamamoto, and R.O.Ryan (2009).
Domain swapping reveals that low density lipoprotein (LDL) type A repeat order affects ligand binding to the LDL receptor.
  J Biol Chem, 284, 13396-13400.  
19583244 Z.Zhao, and P.Michaely (2009).
The role of calcium in lipoprotein release by the low-density lipoprotein receptor.
  Biochemistry, 48, 7313-7324.  
  18626063 A.P.Lillis, L.B.Van Duyn, J.E.Murphy-Ullrich, and D.K.Strickland (2008).
LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies.
  Physiol Rev, 88, 887-918.  
18997008 C.Rankl, F.Kienberger, L.Wildling, J.Wruss, H.J.Gruber, D.Blaas, and P.Hinterdorfer (2008).
Multiple receptors involved in human rhinovirus attachment to live cells.
  Proc Natl Acad Sci U S A, 105, 17778-17783.  
17694547 R.Li, and S.W.Morris (2008).
Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy.
  Med Res Rev, 28, 372-412.  
18677035 Z.Zhao, and P.Michaely (2008).
The epidermal growth factor homology domain of the LDL receptor drives lipoprotein release through an allosteric mechanism involving H190, H562, and H586.
  J Biol Chem, 283, 26528-26537.  
17245526 C.A.Wolf, F.Dancea, M.Shi, V.Bade-Noskova, H.Rüterjans, D.Kerjaschki, and C.Lücke (2007).
Solution structure of the twelfth cysteine-rich ligand-binding repeat in rat megalin.
  J Biomol NMR, 37, 321-328.
PDB code: 2i1p
16301204 K.Arnold, L.Bordoli, J.Kopp, and T.Schwede (2006).
The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling.
  Bioinformatics, 22, 195-201.  
16736493 K.Pääkkönen, H.Tossavainen, P.Permi, H.Rakkolainen, H.Rauvala, E.Raulo, I.Kilpeläinen, and P.Güntert (2006).
Solution structures of the first and fourth TSR domains of F-spondin.
  Proteins, 64, 665-672.
PDB codes: 1szl 1vex
15952897 H.Jeon, and S.C.Blacklow (2005).
Structure and physiologic function of the low-density lipoprotein receptor.
  Annu Rev Biochem, 74, 535-562.  
15950875 N.Beglova, and S.C.Blacklow (2005).
The LDL receptor: how acid pulls the trigger.
  Trends Biochem Sci, 30, 309-317.  
16282495 T.Rai, M.Caffrey, and L.Rong (2005).
Identification of two residues within the LDL-A module of Tva that dictate the altered receptor specificity of mutant subgroup A avian sarcoma and leukosis viruses.
  J Virol, 79, 14962-14966.  
15095281 K.Pulford, S.W.Morris, and F.Turturro (2004).
Anaplastic lymphoma kinase proteins in growth control and cancer.
  J Cell Physiol, 199, 330-358.  
15146486 M.Prévost, and V.Raussens (2004).
Apolipoprotein E-low density lipoprotein receptor binding: study of protein-protein interaction in rationally selected docked complexes.
  Proteins, 55, 874-884.  
15064754 N.Verdaguer, I.Fita, M.Reithmayer, R.Moser, and D.Blaas (2004).
X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein.
  Nat Struct Mol Biol, 11, 429-434.
PDB code: 1v9u
14694099 T.Rai, D.Marble, K.Rihani, and L.Rong (2004).
The spacing between cysteines two and three of the LDL-A module of Tva is important for subgroup A avian sarcoma and leukosis virus entry.
  J Virol, 78, 683-691.  
12603605 A.Orren, A.M.O'Hara, B.P.Morgan, A.P.Moran, and R.Würzner (2003).
An abnormal but functionally active complement component C9 protein found in an Irish family with subtotal C9 deficiency.
  Immunology, 108, 384-390.  
12942512 C.S.Lee, J.H.Han, S.M.Lee, J.S.Hwang, S.W.Kang, B.H.Lee, and H.R.Kim (2003).
Wax moth, Galleria mellonella fat body receptor for high-density lipophorin (HDLp).
  Arch Insect Biochem Physiol, 54, 14-24.  
14675545 G.Rudenko, and J.Deisenhofer (2003).
The low-density lipoprotein receptor: ligands, debates and lore.
  Curr Opin Struct Biol, 13, 683-689.  
14573953 G.Rudenko, L.Henry, C.Vonrhein, G.Bricogne, and J.Deisenhofer (2003).
'MAD'ly phasing the extracellular domain of the LDL receptor: a medium-sized protein, large tungsten clusters and multiple non-isomorphous crystals.
  Acta Crystallogr D Biol Crystallogr, 59, 1978-1986.  
12072496 M.Reithmayer, A.Reischl, L.Snyers, and D.Blaas (2002).
Species-specific receptor recognition by a minor-group human rhinovirus (HRV): HRV serotype 1A distinguishes between the murine and the human low-density lipoprotein receptor.
  J Virol, 76, 6957-6965.  
12381843 Q.Y.Wang, B.Manicassamy, X.Yu, K.Dolmer, P.G.Gettins, and L.Rong (2002).
Characterization of the LDL-A module mutants of Tva, the subgroup A Rous sarcoma virus receptor, and the implications in protein folding.
  Protein Sci, 11, 2596-2605.  
11861852 Q.Y.Wang, W.Huang, K.Dolmer, P.G.Gettins, and L.Rong (2002).
Solution structure of the viral receptor domain of Tva and its implications in viral entry.
  J Virol, 76, 2848-2856.
PDB code: 1jrf
11442633 C.E.Lorén, A.Scully, C.Grabbe, P.T.Edeen, J.Thomas, M.McKeown, T.Hunter, and R.H.Palmer (2001).
Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo.
  Genes Cells, 6, 531-544.  
11258891 N.Beglova, C.L.North, and S.C.Blacklow (2001).
Backbone dynamics of a module pair from the ligand-binding domain of the LDL receptor.
  Biochemistry, 40, 2808-2815.  
11160709 Q.Y.Wang, K.Dolmer, W.Huang, P.G.Gettins, and L.Rong (2001).
Role of calcium in protein folding and function of Tva, the receptor of subgroup A avian sarcoma and leukosis virus.
  J Virol, 75, 2051-2058.  
10704205 C.L.North, and S.C.Blacklow (2000).
Solution structure of the sixth LDL-A module of the LDL receptor.
  Biochemistry, 39, 2564-2571.
PDB code: 1d2j
11101504 E.A.Hewat, E.Neumann, J.F.Conway, R.Moser, B.Ronacher, T.C.Marlovits, and D.Blaas (2000).
The cellular receptor to human rhinovirus 2 binds around the 5-fold axis and not in the canyon: a structural view.
  EMBO J, 19, 6317-6325.  
10727470 L.Li, X.Zhang, S.Kovacic, A.J.Long, K.Bourque, C.R.Wood, and Y.S.Choi (2000).
Identification of a human follicular dendritic cell molecule that stimulates germinal center B cell growth.
  J Exp Med, 191, 1077-1084.  
  10933493 N.D.Kurniawan, A.R.Atkins, S.Bieri, C.J.Brown, I.M.Brereton, P.A.Kroon, and R.Smith (2000).
NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor.
  Protein Sci, 9, 1282-1293.
PDB code: 1f5y
10978145 O.M.Andersen, P.A.Christensen, L.L.Christensen, C.Jacobsen, S.K.Moestrup, M.Etzerodt, and H.C.Thogersen (2000).
Specific binding of alpha-macroglobulin to complement-type repeat CR4 of the low-density lipoprotein receptor-related protein.
  Biochemistry, 39, 10627-10633.  
10194304 C.L.North, and S.C.Blacklow (1999).
Structural independence of ligand-binding modules five and six of the LDL receptor.
  Biochemistry, 38, 3926-3935.  
  10493581 D.Clayton, I.M.Brereton, P.A.Kroon, and R.Smith (1999).
NMR studies of the low-density lipoprotein receptor-binding peptide of apolipoprotein E bound to dodecylphosphocholine micelles.
  Protein Sci, 8, 1797-1805.  
  10074155 J.W.Balliet, J.Berson, C.M.D'Cruz, J.Huang, J.Crane, J.M.Gilbert, and P.Bates (1999).
Production and characterization of a soluble, active form of Tva, the subgroup A avian sarcoma and leukosis virus receptor.
  J Virol, 73, 3054-3061.  
10448520 M.M.Hussain, D.K.Strickland, and A.Bakillah (1999).
The mammalian low-density lipoprotein receptor family.
  Annu Rev Nutr, 19, 141-172.  
10089402 S.Trakhanov, S.Parkin, R.Raffaï, R.Milne, Y.M.Newhouse, K.H.Weisgraber, and B.Rupp (1999).
Structure of a monoclonal 2E8 Fab antibody fragment specific for the low-density lipoprotein-receptor binding region of apolipoprotein E refined at 1.9 A.
  Acta Crystallogr D Biol Crystallogr, 55, 122-128.
PDB code: 12e8
9484237 A.R.Atkins, I.M.Brereton, P.A.Kroon, H.T.Lee, and R.Smith (1998).
Calcium is essential for the structural integrity of the cysteine-rich, ligand-binding repeat of the low-density lipoprotein receptor.
  Biochemistry, 37, 1662-1670.  
9760226 D.Chamberlain, C.G.Ullman, and S.J.Perkins (1998).
Possible arrangement of the five domains in human complement factor I as determined by a combination of X-ray and neutron scattering and homology modeling.
  Biochemistry, 37, 13918-13929.  
9700498 I.D.Campbell (1998).
The modular architecture of leukocyte cell-surface receptors.
  Immunol Rev, 163, 11-18.  
9556295 J.Hasler-Rapacz, H.Ellegren, A.K.Fridolfsson, B.Kirkpatrick, S.Kirk, L.Andersson, and J.Rapacz (1998).
Identification of a mutation in the low density lipoprotein receptor gene associated with recessive familial hypercholesterolemia in swine.
  Am J Med Genet, 76, 379-386.  
9836596 K.Dolmer, W.Huang, and P.G.Gettins (1998).
Characterization of the calcium site in two complement-like domains from the low-density lipoprotein receptor-related protein (LRP) and comparison with a repeat from the low-density lipoprotein receptor.
  Biochemistry, 37, 17016-17023.  
9634697 L.Jenner, L.Husted, S.Thirup, L.Sottrup-Jensen, and J.Nyborg (1998).
Crystal structure of the receptor-binding domain of alpha 2-macroglobulin.
  Structure, 6, 595-604.
PDB code: 1ayo
  9573218 L.Rong, K.Gendron, B.Strohl, R.Shenoy, R.J.Wool-Lewis, and P.Bates (1998).
Characterization of determinants for envelope binding and infection in tva, the subgroup A avian sarcoma and leukosis virus receptor.
  J Virol, 72, 4552-4559.  
9671701 L.Rong, K.Gendron, and P.Bates (1998).
Conversion of a human low-density lipoprotein receptor ligandbinding repeat to a virus receptor: identification of residues important for ligand specificity.
  Proc Natl Acad Sci U S A, 95, 8467-8472.  
9692993 S.Bieri, A.R.Atkins, H.T.Lee, D.J.Winzor, R.Smith, and P.A.Kroon (1998).
Folding, calcium binding, and structural characterization of a concatemer of the first and second ligand-binding modules of the low-density lipoprotein receptor.
  Biochemistry, 37, 10994-11002.  
9541543 T.W.Sappington, and A.S.Raikhel (1998).
Ligand-binding domains in vitellogenin receptors and other LDL-receptor family members share a common ancestral ordering of cysteine-rich repeats.
  J Mol Evol, 46, 476-487.  
  9865955 W.Huang, K.Dolmer, X.Liao, and P.G.Gettins (1998).
Localization of basic residues required for receptor binding to the single alpha-helix of the receptor binding domain of human alpha2-macroglobulin.
  Protein Sci, 7, 2602-2612.  
8945512 J.Brojatsch, J.Naughton, M.M.Rolls, K.Zingler, and J.A.Young (1996).
CAR1, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis-sarcoma viruses and mediates apoptosis.
  Cell, 87, 845-855.  
8706711 J.T.Djordjevic, S.Bieri, R.Smith, and P.A.Kroon (1996).
A deletion in the first cysteine-rich repeat of the low-density-lipoprotein receptor leads to the formation of multiple misfolded isomers.
  Eur J Biochem, 239, 214-219.  
  8892869 K.Zingler, and J.A.Young (1996).
Residue Trp-48 of Tva is critical for viral entry but not for high-affinity binding to the SU glycoprotein of subgroup A avian leukosis and sarcoma viruses.
  J Virol, 70, 7510-7516.  
8870072 P.Bork, A.K.Downing, B.Kieffer, and I.D.Campbell (1996).
Structure and distribution of modules in extracellular proteins.
  Q Rev Biophys, 29, 119-167.  
8784348 S.C.Blacklow, and P.S.Kim (1996).
Protein folding and calcium binding defects arising from familial hypercholesterolemia mutations of the LDL receptor.
  Nat Struct Biol, 3, 758-762.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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