 |
PDBsum entry 1ldr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Binding protein
|
PDB id
|
|
|
|
1ldr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Biochemistry
34:14474-14481
(1995)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
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
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
H.Jeon,
and
S.C.Blacklow
(2005).
Structure and physiologic function of the low-density lipoprotein receptor.
|
| |
Annu Rev Biochem,
74,
535-562.
|
|
|
|
|
|
|
N.Beglova,
and
S.C.Blacklow
(2005).
The LDL receptor: how acid pulls the trigger.
|
| |
Trends Biochem Sci,
30,
309-317.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
G.Rudenko,
and
J.Deisenhofer
(2003).
The low-density lipoprotein receptor: ligands, debates and lore.
|
| |
Curr Opin Struct Biol,
13,
683-689.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
J.H.Naismith,
and
S.R.Sprang
(1998).
Modularity in the TNF-receptor family.
|
| |
Trends Biochem Sci,
23,
74-79.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
P.A.Kroon
(1997).
Cholesterol and atherosclerosis.
|
| |
Aust N Z J Med,
27,
492-496.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
Links
