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PDBsum entry 1d2l
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Signaling protein PDB id
1d2l

 

 

 

 

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Contents
Protein chain
45 a.a. *
Metals
_CA
* Residue conservation analysis
PDB id:
1d2l
Name: Signaling protein
Title: Nmr solution structure of complement-like repeat cr3 from the low density lipoprotein receptor-related protein (lrp). Evidence for specific binding to the receptor binding domain of human alpha-2 macroglobulin
Structure: Lipoprotein receptor related protein. Chain: a. Fragment: complement-like repeat 3 (cr3). Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: liver. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: K.Dolmer,W.Huang,P.G.W.Gettins
Key ref:
K.Dolmer et al. (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. PubMed id: 10652313 DOI: 10.1074/jbc.275.5.3264
Date:
24-Sep-99     Release date:   14-Jan-00    
PROCHECK
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 Headers
 References

Protein chain
Q07954  (LRP1_HUMAN) -  Prolow-density lipoprotein receptor-related protein 1 from Homo sapiens
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Seq:
Struc: 		4544 a.a.
45 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
DOI no: 10.1074/jbc.275.5.3264 J Biol Chem 275:3264-3269 (2000)
PubMed id: 10652313  
 
 
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.
K.Dolmer, W.Huang, P.G.Gettins.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Primary structures of complement-like repeats from cluster II of human LRP. Residues Gln 833 (residue 5 of CR3) to Asp1163 of LRP are aligned based on the positions of the conserved six cysteines present in each complement-like repeat of this cluster. The numbering is for the CR3 construct used in the present study, which also contains the residues GSPP prior to the sequence in the figure; with GS (residues 1 and 2) arising as a result of the glutathione S-transferase fusion protein cleavage site and not being present in LRP. Residues that are shaded are those that have been shown to coordinate the calcium in LB5 from LDLR (23) and in CR3 and CR8 from LRP. These are entirely conserved within this cluster, with the exception of CR10, which has K in place of W at position 23. 		Figure 2.
Fig. 2. NMR structures of CR3. Left side, stereo view of 20 best structures of CR3. Right side, ribbon representation of CR3 showing proposed location of the calcium binding site (green sphere).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 3264-3269) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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.  
19439404 J.K.Jensen, K.Dolmer, and P.G.Gettins (2009).
Specificity of binding of the low density lipoprotein receptor-related protein to different conformational states of the clade E serpins plasminogen activator inhibitor-1 and proteinase nexin-1.
  J Biol Chem, 284, 17989-17997.  
  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.  
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
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.  
15731243 S.E.Delos, J.A.Godby, and J.M.White (2005).
Receptor-induced conformational changes in the SU subunit of the avian sarcoma/leukosis virus A envelope protein: implications for fusion activation.
  J Virol, 79, 3488-3499.  
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.  
14613104 O.M.Andersen, and H.H.Petersen (2003).
New light on a long-known protein family.
  Chembiochem, 4, 1137-1146.  
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
11606746 E.De Gregorio, P.T.Spellman, G.M.Rubin, and B.Lemaitre (2001).
Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays.
  Proc Natl Acad Sci U S A, 98, 12590-12595.  
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.  
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.  
  11106161 T.Xiao, D.L.DeCamp, and S.R.Spran (2000).
Structure of a rat alpha 1-macroglobulin receptor-binding domain dimer.
  Protein Sci, 9, 1889-1897.
PDB code: 1edy
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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