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PDBsum entry 1ldr

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protein links
Binding protein PDB id
1ldr
Jmol
Contents
Protein chain
41 a.a. *
* Residue conservation analysis
PDB id:
1ldr
Name: Binding protein
Title: Second repeat of the ldl receptor ligand-binding domain
Structure: Low-density lipoprotein receptor. Chain: a. Fragment: ligand-binding domain, second repeat. Synonym: lb2. 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,J.T.Djordjevic,P.A.Kroon,R.Smith
Key ref:
N.L.Daly et al. (1995). Three-dimensional structure of the second cysteine-rich repeat from the human low-density lipoprotein receptor. Biochemistry, 34, 14474-14481. PubMed id: 7578052
Date:
17-Aug-95     Release date:   08-Mar-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 

 
Biochemistry 34:14474-14481 (1995)
PubMed id: 7578052  
 
 
Three-dimensional structure of the second cysteine-rich repeat from the human low-density lipoprotein receptor.
N.L.Daly, J.T.Djordjevic, P.A.Kroon, R.Smith.
 
  ABSTRACT  
 
The ligand-binding domain of the low-density lipoprotein receptor comprises seven cysteine-rich repeats, which have been highly conserved through evolution. This domain mediates interactions of the receptor with two lipoprotein apoproteins, apo E and apo B-100, putatively through a calcium-dependent association of the ligands with a cluster of acidic residues on the receptor. The second repeat (rLB2) of the receptor binding domain has been expressed as a thrombin-cleavable GST fusion protein, cleaved, and purified. On oxidation the protein refolded to give a single peak on reverse-phase HPLC. The aqueous solution structure of rLB2 has been determined using two-dimensional 1H NMR spectroscopy. In contrast to the amino-terminal repeat, rLB1, rLB2 has a very flexible structure in water. However, the conformation of rLB2 is markedly more ordered in the presence of a 4-fold molar excess of calcium chloride; the proton resonance dispersion and the number of NOESY cross-peaks are greatly enhanced. The three-dimensional structure of rLB2, obtained from the NMR data by molecular geometry and restrained molecular dynamics methods, parallels that of rLB1, with an amino-terminal hairpin structure followed by a succession of turns. However, there are clear differences in the backbone topology and structural flexibility. As for rLB1, the acidic residues are clustered on one face of the module. The side chain of Asp 37, which is part of a completely conserved SDE sequence thought to be involved in ligand binding, is buried, as is its counterpart (Asp 36) in rLB1. These results provide the first experimental support for the hypothesis that each of the repeats in the ligand-binding domain has a similar global fold but also highlight significant differences in structure and internal dynamics.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
  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.  
18343813 X.Arias-Moreno, J.L.Arolas, F.X.Aviles, J.Sancho, and S.Ventura (2008).
Scrambled isomers as key intermediates in the oxidative folding of ligand binding module 5 of the low density lipoprotein receptor.
  J Biol Chem, 283, 13627-13637.  
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
17148455 E.J.Hopkins, S.Layfield, T.Ferraro, R.A.Bathgate, and P.R.Gooley (2007).
The NMR solution structure of the relaxin (RXFP1) receptor lipoprotein receptor class A module and identification of key residues in the N-terminal region of the module that mediate receptor activation.
  J Biol Chem, 282, 4172-4184.
PDB code: 2jm4
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
16769730 S.Contreras-Alcantara, J.A.Godby, and S.E.Delos (2006).
The single ligand-binding repeat of Tva, a low density lipoprotein receptor-related protein, contains two ligand-binding surfaces.
  J Biol Chem, 281, 22827-22838.  
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.  
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.  
12429745 A.Li, M.Sadasivam, and J.L.Ding (2003).
Receptor-ligand interaction between vitellogenin receptor (VtgR) and vitellogenin (Vtg), implications on low density lipoprotein receptor and apolipoprotein B/E. The first three ligand-binding repeats of VtgR interact with the amino-terminal region of Vtg.
  J Biol Chem, 278, 2799-2806.  
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.  
12459547 G.Rudenko, L.Henry, K.Henderson, K.Ichtchenko, M.S.Brown, J.L.Goldstein, and J.Deisenhofer (2002).
Structure of the LDL receptor extracellular domain at endosomal pH.
  Science, 298, 2353-2358.
PDB code: 1n7d
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
12036962 V.Raussens, C.M.Slupsky, R.O.Ryan, and B.D.Sykes (2002).
NMR structure and dynamics of a receptor-active apolipoprotein E peptide.
  J Biol Chem, 277, 29172-29180.  
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.  
10652313 K.Dolmer, W.Huang, and P.G.Gettins (2000).
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, 275, 3264-3269.
PDB code: 1d2l
  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.  
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
10318830 W.Huang, K.Dolmer, and P.G.Gettins (1999).
NMR solution structure of complement-like repeat CR8 from the low density lipoprotein receptor-related protein.
  J Biol Chem, 274, 14130-14136.
PDB codes: 1bv8 1cr8
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.  
9538693 J.H.Naismith, and S.R.Sprang (1998).
Modularity in the TNF-receptor family.
  Trends Biochem Sci, 23, 74-79.  
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.  
  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.  
  9448903 P.A.Kroon (1997).
Cholesterol and atherosclerosis.
  Aust N Z J Med, 27, 492-496.  
9325268 T.Simmons, Y.M.Newhouse, K.S.Arnold, T.L.Innerarity, and K.H.Weisgraber (1997).
Human low density lipoprotein receptor fragment. Successful refolding of a functionally active ligand-binding domain produced in Escherichia coli.
  J Biol Chem, 272, 25531-25536.  
  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.  
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 code is shown on the right.