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Signaling protein PDB id
1j8e
Jmol
Contents
Protein chain
44 a.a. *
Metals
_CA
Waters ×31
* Residue conservation analysis
PDB id:
1j8e
Name: Signaling protein
Title: Crystal structure of ligand-binding repeat cr7 from lrp
Structure: Low-density lipoprotein receptor-related protein 1. Chain: a. Fragment: complement-like repeat 7 (cr7), ldl-receptor class a 7. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.85Å     R-factor:   0.186     R-free:   0.222
Authors: M.Simonovic,K.Dolmer,W.Huang,D.K.Strickland,K.Volz, P.G.W.Gettins
Key ref:
M.Simonovic et al. (2001). Calcium coordination and pH dependence of the calcium affinity of ligand-binding repeat CR7 from the LRP. Comparison with related domains from the LRP and the LDL receptor. Biochemistry, 40, 15127-15134. PubMed id: 11735395 DOI: 10.1021/bi015688m
Date:
21-May-01     Release date:   19-Dec-01    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q07954  (LRP1_HUMAN) -  Prolow-density lipoprotein receptor-related protein 1
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		4544 a.a.
44 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1021/bi015688m Biochemistry 40:15127-15134 (2001)
PubMed id: 11735395  
 
 
Calcium coordination and pH dependence of the calcium affinity of ligand-binding repeat CR7 from the LRP. Comparison with related domains from the LRP and the LDL receptor.
M.Simonovic, K.Dolmer, W.Huang, D.K.Strickland, K.Volz, P.G.Gettins.
 
  ABSTRACT  
 
We have determined the X-ray crystal structure to 1.8 A resolution of the Ca(2+) complex of complement-like repeat 7 (CR7) from the low-density lipoprotein receptor-related protein (LRP) and characterized its calcium binding properties at pH 7.4 and 5. CR7 occurs in a region of the LRP that binds to the receptor-associated protein, RAP, and other protein ligands in a Ca(2+)-dependent manner. The calcium coordination is identical to that found in LB5 and consists of carboxyls from three conserved aspartates and one conserved glutamate, and the backbone carbonyls of a tryptophan and another aspartate. The overall fold of CR7 is similar to those of CR3 and CR8 from the LRP and LB5 from the LDL receptor, though the low degree of sequence homology of residues not involved in calcium coordination or in disulfide formation results in a distinct pattern of surface residues for each domain, including CR7. The thermodynamic parameters for Ca(2+) binding at both extracellular and endosomal pHs were determined by isothermal titration calorimetry for CR7 and for related complement-like repeats CR3, CR8, and LB5. Although the drop in pH resulted in a reduction in calcium affinity in each case, the changes were very variable in magnitude, being as low as a 2-fold reduction for CR3. This suggests that a pH-dependent change in calcium affinity alone cannot be responsible for the release of bound protein ligands from the LRP at the pH prevailing in the endosome, which in turn requires one or more other pH-dependent effects for regulating protein ligand release.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20030366 M.Guttman, J.H.Prieto, J.E.Croy, and E.A.Komives (2010).
Decoding of lipoprotein-receptor interactions: properties of ligand binding modules governing interactions with apolipoprotein E.
  Biochemistry, 49, 1207-1216.  
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
19674976 S.Huang, L.Henry, Y.K.Ho, H.J.Pownall, and G.Rudenko (2010).
Mechanism of LDL binding and release probed by structure-based mutagenesis of the LDL receptor.
  J Lipid Res, 51, 297-308.  
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.  
19397492 J.K.Jensen, K.Dolmer, C.Schar, and P.G.Gettins (2009).
Receptor-associated protein (RAP) has two high-affinity binding sites for the low-density lipoprotein receptor-related protein (LRP): consequences for the chaperone functions of RAP.
  Biochem J, 421, 273-282.  
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.  
18331356 S.D.Roosendaal, J.Kerver, M.Schipper, K.W.Rodenburg, and D.J.Van der Horst (2008).
The complex of the insect LDL receptor homolog, lipophorin receptor, LpR, and its lipoprotein ligand does not dissociate under endosomal conditions.
  FEBS J, 275, 1751-1766.  
18574243 X.Arias-Moreno, A.Velazquez-Campoy, J.C.Rodríguez, M.Pocoví, and J.Sancho (2008).
Mechanism of low density lipoprotein (LDL) release in the endosome: implications of the stability and Ca2+ affinity of the fifth binding module of the LDL receptor.
  J Biol Chem, 283, 22670-22679.  
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
16838215 C.Chabasse, X.Bailly, S.Sanchez, M.Rousselot, and F.Zal (2006).
Gene structure and molecular phylogeny of the linker chains from the giant annelid hexagonal bilayer hemoglobins.
  J Mol Evol, 63, 365-374.  
16982616 K.Dolmer, and P.G.Gettins (2006).
Three complement-like repeats compose the complete alpha2-macroglobulin binding site in the second ligand binding cluster of the low density lipoprotein receptor-related protein.
  J Biol Chem, 281, 34189-34196.  
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.  
15194751 B.Herdy, L.Snyers, M.Reithmayer, P.Hinterdorfer, and D.Blaas (2004).
Identification of the human rhinovirus serotype 1A binding site on the murine low-density lipoprotein receptor by using human-mouse receptor chimeras.
  J Virol, 78, 6766-6774.  
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.  
14749324 Y.Guo, X.Yu, K.Rihani, Q.Y.Wang, and L.Rong (2004).
The role of a conserved acidic residue in calcium-dependent protein folding for a low density lipoprotein (LDL)-A module: implications in structure and function for the LDL receptor superfamily.
  J Biol Chem, 279, 16629-16637.  
14675545 G.Rudenko, and J.Deisenhofer (2003).
The low-density lipoprotein receptor: ligands, debates and lore.
  Curr Opin Struct Biol, 13, 683-689.  
12921543 O.M.Andersen, H.Vorum, B.Honoré, and H.C.Thøgersen (2003).
Ca2+ binding to complement-type repeat domains 5 and 6 from the low-density lipoprotein receptor-related protein.
  BMC Biochem, 4, 7.  
14661984 S.Mehboob, J.Jacob, M.May, L.Kotula, P.Thiyagarajan, M.E.Johnson, and L.W.Fung (2003).
Structural analysis of the alpha N-terminal region of erythroid and nonerythroid spectrins by small-angle X-ray scattering.
  Biochemistry, 42, 14702-14710.  
12805452 X.Yu, Q.Y.Wang, Y.Guo, K.Dolmer, J.A.Young, P.G.Gettins, and L.Rong (2003).
Kinetic analysis of binding interaction between the subgroup A Rous sarcoma virus glycoprotein SU and its cognate receptor Tva: calcium is not required for ligand binding.
  J Virol, 77, 7517-7526.  
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.  
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.