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PDBsum entry 1n7d
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Lipid transport
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PDB id
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1n7d
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Contents |
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* Residue conservation analysis
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DOI no:
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Science
298:2353-2358
(2002)
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PubMed id:
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Structure of the LDL receptor extracellular domain at endosomal pH.
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G.Rudenko,
L.Henry,
K.Henderson,
K.Ichtchenko,
M.S.Brown,
J.L.Goldstein,
J.Deisenhofer.
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ABSTRACT
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The low-density lipoprotein receptor mediates cholesterol homeostasis through
endocytosis of lipoproteins. It discharges its ligand in the endosome at pH <
6. In the crystal structure at pH = 5.3, the ligand-binding domain (modules R2
to R7) folds back as an arc over the epidermal growth factor precursor homology
domain (the modules A, B, beta propeller, and C). The modules R4 and R5, which
are critical for lipoprotein binding, associate with the beta propeller via
their calcium-binding loop. We propose a mechanism for lipoprotein release in
the endosome whereby the beta propeller functions as an alternate substrate for
the ligand-binding domain, binding in a calcium-dependent way and promoting
lipoprotein release.
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Selected figure(s)
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Figure 2.
Fig. 2. Two monomers stabilized by tungsten clusters; the
ligand-binding domains have been labeled R2 to R7 and R2* to
R7*, respectively. The linkers between R4 and R5 and R4* and R5*
meet at a crystallographic twofold axis. At a distance below, a
cluster (center) sits on the twofold as well.
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Figure 3.
Fig. 3. Interface formed between R4, R5, and  propeller.
Residues discussed in the text are shown and labeled except for
Ser191, which was omitted for clarity. R4, magenta trace; R5,
red trace; propeller,
cyan trace; and calcium ions, maroon spheres.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2002,
298,
2353-2358)
copyright 2002.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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L.Zhang,
J.Song,
G.Cavigiolio,
B.Y.Ishida,
S.Zhang,
J.P.Kane,
K.H.Weisgraber,
M.N.Oda,
K.A.Rye,
H.J.Pownall,
and
G.Ren
(2011).
Morphology and structure of lipoproteins revealed by an optimized negative-staining protocol of electron microscopy.
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J Lipid Res,
52,
175-184.
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M.R.Rivero,
S.L.Miras,
R.Quiroga,
A.S.Rópolo,
and
M.C.Touz
(2011).
Giardia lamblia low-density lipoprotein receptor-related protein is involved in selective lipoprotein endocytosis and parasite replication.
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Mol Microbiol,
79,
1204-1219.
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M.van den Biggelaar,
E.Sellink,
J.W.Klein Gebbinck,
K.Mertens,
and
A.B.Meijer
(2011).
A single lysine of the two-lysine recognition motif of the D3 domain of receptor-associated protein is sufficient to mediate endocytosis by low-density lipoprotein receptor-related protein.
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Int J Biochem Cell Biol,
43,
431-440.
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P.S.Hauser,
V.Narayanaswami,
and
R.O.Ryan
(2011).
Apolipoprotein E: from lipid transport to neurobiology.
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Prog Lipid Res,
50,
62-74.
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Z.Cheng,
T.Biechele,
Z.Wei,
S.Morrone,
R.T.Moon,
L.Wang,
and
W.Xu
(2011).
Crystal structures of the extracellular domain of LRP6 and its complex with DKK1.
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Nat Struct Mol Biol,
18,
1204-1210.
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PDB codes:
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G.Ren,
G.Rudenko,
S.J.Ludtke,
J.Deisenhofer,
W.Chiu,
and
H.J.Pownall
(2010).
Model of human low-density lipoprotein and bound receptor based on cryoEM.
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Proc Natl Acad Sci U S A,
107,
1059-1064.
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H.Liu,
Z.S.Juo,
A.H.Shim,
P.J.Focia,
X.Chen,
K.C.Garcia,
and
X.He
(2010).
Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1.
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Cell,
142,
749-761.
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PDB codes:
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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.
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Biochemistry,
49,
1207-1216.
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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.
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J Mol Biol,
398,
306-319.
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PDB codes:
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N.Yasui,
T.Nogi,
and
J.Takagi
(2010).
Structural basis for specific recognition of reelin by its receptors.
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Structure,
18,
320-331.
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PDB code:
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R.Fuchs,
and
D.Blaas
(2010).
Uncoating of human rhinoviruses.
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Rev Med Virol,
20,
281-297.
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S.A.Ettenberg,
O.Charlat,
M.P.Daley,
S.Liu,
K.J.Vincent,
D.D.Stuart,
A.G.Schuller,
J.Yuan,
B.Ospina,
J.Green,
Q.Yu,
R.Walsh,
S.Li,
R.Schmitz,
H.Heine,
S.Bilic,
L.Ostrom,
R.Mosher,
K.F.Hartlepp,
Z.Zhu,
S.Fawell,
Y.M.Yao,
D.Stover,
P.M.Finan,
J.A.Porter,
W.R.Sellers,
I.M.Klagge,
and
F.Cong
(2010).
Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies.
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Proc Natl Acad Sci U S A,
107,
15473-15478.
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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.
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J Lipid Res,
51,
297-308.
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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.
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Proteins,
78,
950-961.
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A.F.Doubleday,
F.A.Kaestle,
L.A.Cox,
S.Birnbaum,
M.C.Mahaney,
and
L.M.Havill
(2009).
LRP5 sequence and polymorphisms in the baboon.
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J Med Primatol,
38,
97.
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A.Sivashanmugam,
and
J.Wang
(2009).
A unified scheme for initiation and conformational adaptation of human apolipoprotein E N-terminal domain upon lipoprotein binding and for receptor binding activity.
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J Biol Chem,
284,
14657-14666.
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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.
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Proteins,
77,
940-949.
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D.J.Van der Horst,
S.D.Roosendaal,
and
K.W.Rodenburg
(2009).
Circulatory lipid transport: lipoprotein assembly and function from an evolutionary perspective.
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Mol Cell Biochem,
326,
105-119.
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J.D.Horton,
J.C.Cohen,
and
H.H.Hobbs
(2009).
PCSK9: a convertase that coordinates LDL catabolism.
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J Lipid Res,
50,
S172-S177.
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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.
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Biochem J,
421,
273-282.
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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.
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J Biol Chem,
284,
17989-17997.
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M.C.McNutt,
H.J.Kwon,
C.Chen,
J.R.Chen,
J.D.Horton,
and
T.A.Lagace
(2009).
Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells.
|
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J Biol Chem,
284,
10561-10570.
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PDB codes:
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M.E.Binnerts,
N.Tomasevic,
J.M.Bright,
J.Leung,
V.E.Ahn,
K.A.Kim,
X.Zhan,
S.Liu,
S.Yonkovich,
J.Williams,
M.Zhou,
D.Gros,
M.Dixon,
W.Korver,
W.I.Weis,
and
A.Abo
(2009).
The first propeller domain of LRP6 regulates sensitivity to DKK1.
|
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Mol Biol Cell,
20,
3552-3560.
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P.S.Hauser,
V.Raussens,
T.Yamamoto,
G.E.Abdullahi,
P.M.Weers,
B.D.Sykes,
and
R.O.Ryan
(2009).
Semisynthesis and segmental isotope labeling of the apoE3 N-terminal domain using expressed protein ligation.
|
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J Lipid Res,
50,
1548-1555.
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T.Konecsni,
U.Berka,
A.Pickl-Herk,
G.Bilek,
A.G.Khan,
L.Gajdzig,
R.Fuchs,
and
D.Blaas
(2009).
Low pH-triggered beta-propeller switch of the low-density lipoprotein receptor assists rhinovirus infection.
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J Virol,
83,
10922-10930.
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T.Yamamoto,
and
R.O.Ryan
(2009).
Domain swapping reveals that low density lipoprotein (LDL) type A repeat order affects ligand binding to the LDL receptor.
|
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J Biol Chem,
284,
13396-13400.
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Z.Zhao,
and
P.Michaely
(2009).
The role of calcium in lipoprotein release by the low-density lipoprotein receptor.
|
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Biochemistry,
48,
7313-7324.
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A.Bashan,
and
A.Yonath
(2008).
The linkage between ribosomal crystallography, metal ions, heteropolytungstates and functional flexibility.
|
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J Mol Struct,
890,
289-294.
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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.
|
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Physiol Rev,
88,
887-918.
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A.S.Peterson,
L.G.Fong,
and
S.G.Young
(2008).
PCSK9 function and physiology.
|
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J Lipid Res,
49,
1152-1156.
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C.Rankl,
F.Kienberger,
L.Wildling,
J.Wruss,
H.J.Gruber,
D.Blaas,
and
P.Hinterdorfer
(2008).
Multiple receptors involved in human rhinovirus attachment to live cells.
|
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Proc Natl Acad Sci U S A,
105,
17778-17783.
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D.W.Zhang,
R.Garuti,
W.J.Tang,
J.C.Cohen,
and
H.H.Hobbs
(2008).
Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor.
|
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Proc Natl Acad Sci U S A,
105,
13045-13050.
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E.Sundaramoorthy,
S.Maiti,
S.K.Brahmachari,
and
S.Sengupta
(2008).
Predicting protein homocysteinylation targets based on dihedral strain energy and pKa of cysteines.
|
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Proteins,
71,
1475-1483.
|
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H.J.Kwon,
T.A.Lagace,
M.C.McNutt,
J.D.Horton,
and
J.Deisenhofer
(2008).
Molecular basis for LDL receptor recognition by PCSK9.
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Proc Natl Acad Sci U S A,
105,
1820-1825.
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PDB code:
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J.Su,
N.Zhang,
and
P.C.Ho
(2008).
Evaluation of the pharmacokinetics of all-trans-retinoic acid (ATRA) in Wistar rats after intravenous administration of ATRA loaded into tributyrin submicron emulsion and its cellular activity on caco-2 and HepG2 cell lines.
|
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J Pharm Sci,
97,
2844-2853.
|
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L.Chen,
K.Wang,
Y.Shao,
J.Huang,
X.Li,
J.Shan,
D.Wu,
and
J.J.Zheng
(2008).
Structural insight into the mechanisms of Wnt signaling antagonism by Dkk.
|
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J Biol Chem,
283,
23364-23370.
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PDB code:
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N.M.Ananyeva,
Y.M.Makogonenko,
A.G.Sarafanov,
I.V.Pechik,
N.Gorlatova,
K.P.Radtke,
M.Shima,
and
E.L.Saenko
(2008).
Interaction of coagulation factor VIII with members of the low-density lipoprotein receptor family follows common mechanism and involves consensus residues within the A2 binding site 484-509.
|
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Blood Coagul Fibrinolysis,
19,
543-555.
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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.
|
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FEBS J,
275,
1751-1766.
|
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T.Yamamoto,
H.C.Chen,
E.Guigard,
C.M.Kay,
and
R.O.Ryan
(2008).
Molecular studies of pH-dependent ligand interactions with the low-density lipoprotein receptor.
|
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Biochemistry,
47,
11647-11652.
|
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T.Yamamoto,
H.W.Choi,
and
R.O.Ryan
(2008).
Apolipoprotein E isoform-specific binding to the low-density lipoprotein receptor.
|
| |
Anal Biochem,
372,
222-226.
|
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|
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|
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Z.Zhao,
and
P.Michaely
(2008).
The epidermal growth factor homology domain of the LDL receptor drives lipoprotein release through an allosteric mechanism involving H190, H562, and H586.
|
| |
J Biol Chem,
283,
26528-26537.
|
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|
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D.Cunningham,
D.E.Danley,
K.F.Geoghegan,
M.C.Griffor,
J.L.Hawkins,
T.A.Subashi,
A.H.Varghese,
M.J.Ammirati,
J.S.Culp,
L.R.Hoth,
M.N.Mansour,
K.M.McGrath,
A.P.Seddon,
S.Shenolikar,
K.J.Stutzman-Engwall,
L.C.Warren,
D.Xia,
and
X.Qiu
(2007).
Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia.
|
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Nat Struct Mol Biol,
14,
413-419.
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PDB code:
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D.E.Piper,
S.Jackson,
Q.Liu,
W.G.Romanow,
S.Shetterly,
S.T.Thibault,
B.Shan,
and
N.P.Walker
(2007).
The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol.
|
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Structure,
15,
545-552.
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PDB code:
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D.Lee,
J.D.Walsh,
M.Migliorini,
P.Yu,
T.Cai,
C.D.Schwieters,
S.Krueger,
D.K.Strickland,
and
Y.X.Wang
(2007).
The structure of receptor-associated protein (RAP).
|
| |
Protein Sci,
16,
1628-1640.
|
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PDB codes:
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D.Puett,
Y.Li,
G.DeMars,
K.Angelova,
and
F.Fanelli
(2007).
A functional transmembrane complex: the luteinizing hormone receptor with bound ligand and G protein.
|
| |
Mol Cell Endocrinol,
260,
126-136.
|
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|
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H.Zhu,
H.M.Tucker,
K.E.Grear,
J.F.Simpson,
A.K.Manning,
L.A.Cupples,
and
S.Estus
(2007).
A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol.
|
| |
Hum Mol Genet,
16,
1765-1772.
|
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L.M.Bareford,
and
P.W.Swaan
(2007).
Endocytic mechanisms for targeted drug delivery.
|
| |
Adv Drug Deliv Rev,
59,
748-758.
|
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|
|
|
|
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N.Yasui,
T.Nogi,
T.Kitao,
Y.Nakano,
M.Hattori,
and
J.Takagi
(2007).
Structure of a receptor-binding fragment of reelin and mutational analysis reveal a recognition mechanism similar to endocytic receptors.
|
| |
Proc Natl Acad Sci U S A,
104,
9988-9993.
|
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PDB code:
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S.C.Blacklow
(2007).
Versatility in ligand recognition by LDL receptor family proteins: advances and frontiers.
|
| |
Curr Opin Struct Biol,
17,
419-426.
|
|
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S.Cuesta-López,
F.Falo,
and
J.Sancho
(2007).
Computational diagnosis of protein conformational diseases: short molecular dynamics simulations reveal a fast unfolding of r-LDL mutants that cause familial hypercholesterolemia.
|
| |
Proteins,
66,
87-95.
|
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W.Balemans,
J.P.Devogelaer,
E.Cleiren,
E.Piters,
E.Caussin,
and
W.Van Hul
(2007).
Novel LRP5 missense mutation in a patient with a high bone mass phenotype results in decreased DKK1-mediated inhibition of Wnt signaling.
|
| |
J Bone Miner Res,
22,
708-716.
|
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A.Mylona,
C.Fernández-Tornero,
P.Legrand,
M.Haupt,
A.Sentenac,
J.Acker,
and
C.W.Müller
(2006).
Structure of the tau60/Delta tau91 subcomplex of yeast transcription factor IIIC: insights into preinitiation complex assembly.
|
| |
Mol Cell,
24,
221-232.
|
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PDB code:
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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.
|
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C.Fan,
X.Wo,
Y.Qian,
J.Yin,
and
L.Gao
(2006).
Effect of curcumin on the expression of LDL receptor in mouse macrophages.
|
| |
J Ethnopharmacol,
105,
251-254.
|
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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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|
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