PDBsum entry 1hz8

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protein metals links
Lipid binding protein PDB id
Protein chain
82 a.a. *
_CA ×2
* Residue conservation analysis
PDB id:
Name: Lipid binding protein
Title: Solution structure and backbone dynamics of a concatemer of egf-homology modules of the human low density lipoprotein receptor
Structure: Low density lipoprotein receptor. Chain: a. Fragment: egf-ab concatemer (residues 314-395). Synonym: ldl receptor. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: liver. Expressed in: escherichia coli. Expression_system_taxid: 562. Bl21-de3. Pet-30a+
NMR struc: 30 models
Authors: N.D.Kurniawan,K.Aliabadizadeh,I.M.Brereton,P.A.Kroon,R.Smith
Key ref:
N.D.Kurniawan et al. (2001). NMR structure and backbone dynamics of a concatemer of epidermal growth factor homology modules of the human low-density lipoprotein receptor. J Mol Biol, 311, 341-356. PubMed id: 11478865 DOI: 10.1006/jmbi.2001.4867
23-Jan-01     Release date:   15-Aug-01    
Go to PROCHECK summary

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

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     calcium ion binding     1 term  


DOI no: 10.1006/jmbi.2001.4867 J Mol Biol 311:341-356 (2001)
PubMed id: 11478865  
NMR structure and backbone dynamics of a concatemer of epidermal growth factor homology modules of the human low-density lipoprotein receptor.
N.D.Kurniawan, K.Aliabadizadeh, I.M.Brereton, P.A.Kroon, R.Smith.
The ligand-binding region of the low-density lipoprotein (LDL) receptor is formed by seven N-terminal, imperfect, cysteine-rich (LB) modules. This segment is followed by an epidermal growth factor precursor homology domain with two N-terminal, tandem, EGF-like modules that are thought to participate in LDL binding and recycling of the endocytosed receptor to the cell surface. EGF-A and the concatemer, EGF-AB, of these modules were expressed in Escherichia coli. Correct protein folding of EGF-A and the concatemer EGF-AB was achieved in the presence or absence of calcium ions, in contrast to the LB modules, which require them for correct folding. Homonuclear and heteronuclear 1H-15N NMR spectroscopy at 17.6 T was used to determine the three-dimensional structure of the concatemer. Both modules are formed by two pairs of short, anti-parallel beta-strands. In the concatemer, these modules have a fixed relative orientation, stabilized by calcium ion-binding and hydrophobic interactions at the interface. 15N longitudinal and transverse relaxation rates, and [1H]-15N heteronuclear NOEs were used to derive a model-free description of the backbone dynamics of the molecule. The concatemer appears relatively rigid, particularly near the calcium ion-binding site at the module interface, with an average generalized order parameter of 0.85+/-0.11. Some mutations causing familial hypercholesterolemia may now be rationalized. Mutations of D41, D43 and E44 in the EGF-B calcium ion-binding region may affect the stability of the linker and thus the orientation of the tandem modules. The diminutive core also provides little structural stabilization, necessitating the presence of disulfide bonds. The structure and dynamics of EGF-AB contrast with the N-terminal LB modules, which require calcium ions both for folding to form the correct disulfide connectivities and for maintenance of the folded structure, and are connected by highly mobile linking peptides.
  Selected figure(s)  
Figure 5.
Figure 5. A ribbon diagram showing the secondary structure of EGF-AB. The b-strands are shown with yellow arrows. Two calcium ion sites, located near the N terminus of EGF-A and in the intermodule interface of EGF-AB, are shown with white spheres. The N-terminal EGF-A binding site consists of the carboxyl side-chains of E4 and D18. The aromatic ring of Y23 is involved in calcium binding indirectly by shielding the site from the solvent. The intermodule EGF-AB binding site consists of the backbone carbonyl groups of I42 and L58, the carboxyl side-chains of D41 and E44, and the carbonyl side-chain of N57. The aromatic ring of F31 forms an intermodule interaction with residues E59, G60 and G61 (not labeled for clarity). Y62, which is sequentially equivalent to Y23, is also in close proximity to the calcium ion site but appears not to be involved in the binding. This diagram was produced using Insight98 (Molecular Simulations Inc.).
Figure 8.
Figure 8. (a) Electrostatic surface of EGF-AB, pre- sented in a similar orientation to that in Figure 5. (b) Surface after a 180 ° rotation around the vertical axis in (a). The positively and negatively charged surfaces are shown in blue and red, respectively. These diagrams were produced using Weblab Viewer (Molecular Simu- lations Inc.).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 311, 341-356) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19001363 M.J.Bottomley, A.Cirillo, L.Orsatti, L.Ruggeri, T.S.Fisher, J.C.Santoro, R.T.Cummings, R.M.Cubbon, P.Lo Surdo, A.Calzetta, A.Noto, J.Baysarowich, M.Mattu, F.Talamo, R.De Francesco, C.P.Sparrow, A.Sitlani, and A.Carfí (2009).
Structural and Biochemical Characterization of the Wild Type PCSK9-EGF(AB) Complex and Natural Familial Hypercholesterolemia Mutants.
  J Biol Chem, 284, 1313-1323.
PDB codes: 2w2m 2w2n 2w2o 2w2p 2w2q
18250299 H.J.Kwon, T.A.Lagace, M.C.McNutt, J.D.Horton, and J.Deisenhofer (2008).
Molecular basis for LDL receptor recognition by PCSK9.
  Proc Natl Acad Sci U S A, 105, 1820-1825.
PDB code: 3bps
17452316 D.W.Zhang, T.A.Lagace, R.Garuti, Z.Zhao, M.McDonald, J.D.Horton, J.C.Cohen, and H.H.Hobbs (2007).
Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation.
  J Biol Chem, 282, 18602-18612.  
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.  
15494314 N.Beglova, H.Jeon, C.Fisher, and S.C.Blacklow (2004).
Cooperation between fixed and low pH-inducible interfaces controls lipoprotein release by the LDL receptor.
  Mol Cell, 16, 281-292.
PDB code: 1xfe
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.  
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.  
12511552 R.S.Smallridge, P.Whiteman, J.M.Werner, I.D.Campbell, P.A.Handford, and A.K.Downing (2003).
Solution structure and dynamics of a calcium binding epidermal growth factor-like domain pair from the neonatal region of human fibrillin-1.
  J Biol Chem, 278, 12199-12206.
PDB code: 1lmj
12493918 A.Jansens, E.van Duijn, and I.Braakman (2002).
Coordinated nonvectorial folding in a newly synthesized multidomain protein.
  Science, 298, 2401-2403.  
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
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