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Protein transport
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PDB id
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1py1
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Contents |
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* Residue conservation analysis
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PDB id:
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Protein transport
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Title:
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Complex of gga1-vhs domain and beta-secretasE C-terminal phosphopeptide
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Structure:
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Adp-ribosylation factor binding protein gga1. Chain: a, b, c, d. Fragment: vhs domain (residues 2-157). Synonym: golgi-localized, gamma ear-containing, arf- binding protein 1, gamma-adaptin related protein 1. Engineered: yes. Beta-secretase. Chain: e, f, g, h. Fragment: c-terminus (residues 494-501).
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: gga1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: yes
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Biol. unit:
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Tetramer (from
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Resolution:
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2.60Å
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R-factor:
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0.236
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R-free:
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0.288
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Authors:
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G.Zhu,X.C.Zhang
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Key ref:
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X.He
et al.
(2003).
Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins.
Biochemistry,
42,
12174-12180.
PubMed id:
DOI:
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Date:
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07-Jul-03
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Release date:
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04-Nov-03
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PROCHECK
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Headers
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References
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Q9UJY5
(GGA1_HUMAN) -
ADP-ribosylation factor-binding protein GGA1
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Seq:
Struc:
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639 a.a.
142 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Gene Ontology (GO) functional annotation
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Biological process
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intracellular protein transport
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1 term
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DOI no:
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Biochemistry
42:12174-12180
(2003)
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PubMed id:
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Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins.
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X.He,
G.Zhu,
G.Koelsch,
K.K.Rodgers,
X.C.Zhang,
J.Tang.
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ABSTRACT
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Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease that
initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the
production of amyloid-beta and the onset of Alzheimer's disease (AD). Both
memapsin 2 and APP are transported from the cell surface to endosomes where APP
hydrolysis takes place. Thus, the intracellular transport mechanism of memapsin
2 is important for understanding the pathogenesis of AD. We have previously
shown that the cytosolic domain of memapsin 2 contains an acid-cluster-dileucine
(ACDL) motif that binds the VHS domain of GGA proteins (He et al. (2002) FEBS
Lett. 524, 183-187). This mechanism is the presumed recognition step for the
vesicular packaging of memapsin 2 for its transport to endosomes. The
phosphorylation of a serine residue within the ACDL motif has been reported to
regulate the recycling of memapsin 2 from early endosomes back to the cell
surface. Here, we report a study on the memapsin 2/VHS domain interaction. Using
isothermal titration calorimetry, the dissociation constant, K(d), values are
4.0 x 10(-4), 4.1 x 10(-4), and 3.1 x 10(-4) M for VHS domains from GGA1, GGA2,
and GGA3, respectively. With the serine residue replaced by phosphoserine, the
K(d) decreased about 10-, 4-, and 14-fold for the same three VHS domains. A
crystal structure of the complex between memapsin 2 phosphoserine peptide and
GGA1 VHS was solved at 2.6 A resolution. The side chain of the phosphoserine
group does not interact with the VHS domain but forms an ionic interaction with
the side chain of the C-terminal lysine of the ligand peptide. Energy
calculation of the binding of native and phosphorylated peptides to VHS domains
suggests that this intrapeptide ionic bond in solution may reduce the change in
binding entropy and thus increase binding affinity.
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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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D.W.Klaver,
M.C.Wilce,
H.Cui,
A.C.Hung,
R.Gasperini,
L.Foa,
and
D.H.Small
(2010).
Is BACE1 a suitable therapeutic target for the treatment of Alzheimer's disease? Current strategies and future directions.
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Biol Chem, 391,
849-859.
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A.Elmarghani,
H.Abuabaid,
and
P.Kjellen
(2009).
TOM1L is involved in a novel signaling pathway important for the IL-2 production in Jurkat T cells stimulated by CD3/CD28 co-ligation.
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Mediators Inflamm, 2009,
416298.
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J.Zhang,
A.Gratchev,
V.Riabov,
S.Mamidi,
C.Schmuttermaier,
L.Krusell,
E.Kremmer,
G.Workman,
E.H.Sage,
S.Jalkanen,
S.Goerdt,
and
J.Kzhyshkowska
(2009).
A novel GGA-binding site is required for intracellular sorting mediated by stabilin-1.
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Mol Cell Biol, 29,
6097-6105.
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K.S.Vetrivel,
X.Meckler,
Y.Chen,
P.D.Nguyen,
N.G.Seidah,
R.Vassar,
P.C.Wong,
M.Fukata,
M.Z.Kounnas,
and
G.Thinakaran
(2009).
Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts.
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J Biol Chem, 284,
3793-3803.
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R.Sannerud,
and
W.Annaert
(2009).
Trafficking, a key player in regulated intramembrane proteolysis.
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Semin Cell Dev Biol, 20,
183-190.
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R.Vassar,
D.M.Kovacs,
R.Yan,
and
P.C.Wong
(2009).
The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential.
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J Neurosci, 29,
12787-12794.
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A.K.Ghosh,
S.Gemma,
and
J.Tang
(2008).
beta-Secretase as a therapeutic target for Alzheimer's disease.
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Neurotherapeutics, 5,
399-408.
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I.E.Sánchez,
P.Beltrao,
F.Stricher,
J.Schymkowitz,
J.Ferkinghoff-Borg,
F.Rousseau,
and
L.Serrano
(2008).
Genome-wide prediction of SH2 domain targets using structural information and the FoldX algorithm.
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PLoS Comput Biol, 4,
e1000052.
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R.Boucher,
H.Larkin,
J.Brodeur,
H.Gagnon,
C.Thériault,
and
C.Lavoie
(2008).
Intracellular trafficking of LRP9 is dependent on two acidic cluster/dileucine motifs.
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Histochem Cell Biol, 130,
315-327.
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G.Tesco,
Y.H.Koh,
E.L.Kang,
A.N.Cameron,
S.Das,
M.Sena-Esteves,
M.Hiltunen,
S.H.Yang,
Z.Zhong,
Y.Shen,
J.W.Simpkins,
and
R.E.Tanzi
(2007).
Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity.
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Neuron, 54,
721-737.
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A.Dennes,
C.Cromme,
K.Suresh,
N.S.Kumar,
J.A.Eble,
A.Hahnenkamp,
and
R.Pohlmann
(2005).
The novel Drosophila lysosomal enzyme receptor protein mediates lysosomal sorting in mammalian cells and binds mammalian and Drosophila GGA adaptors.
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J Biol Chem, 280,
12849-12857.
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B.Angeletti,
K.J.Waldron,
K.B.Freeman,
H.Bawagan,
I.Hussain,
C.C.Miller,
K.F.Lau,
M.E.Tennant,
C.Dennison,
N.J.Robinson,
and
C.Dingwall
(2005).
BACE1 cytoplasmic domain interacts with the copper chaperone for superoxide dismutase-1 and binds copper.
|
| |
J Biol Chem, 280,
17930-17937.
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J.Xie,
and
Q.Guo
(2005).
PAR-4 is involved in regulation of beta-secretase cleavage of the Alzheimer amyloid precursor protein.
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J Biol Chem, 280,
13824-13832.
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S.Kametaka,
R.Mattera,
and
J.S.Bonifacino
(2005).
Epidermal growth factor-dependent phosphorylation of the GGA3 adaptor protein regulates its recruitment to membranes.
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Mol Cell Biol, 25,
7988-8000.
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X.He,
F.Li,
W.P.Chang,
and
J.Tang
(2005).
GGA proteins mediate the recycling pathway of memapsin 2 (BACE).
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J Biol Chem, 280,
11696-11703.
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Y.H.Koh,
C.A.von Arnim,
B.T.Hyman,
R.E.Tanzi,
and
G.Tesco
(2005).
BACE is degraded via the lysosomal pathway.
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J Biol Chem, 280,
32499-32504.
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D.J.Owen,
B.M.Collins,
and
P.R.Evans
(2004).
Adaptors for clathrin coats: structure and function.
|
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Annu Rev Cell Dev Biol, 20,
153-191.
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M.J.Cliff,
A.Gutierrez,
and
J.E.Ladbury
(2004).
A survey of the year 2003 literature on applications of isothermal titration calorimetry.
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J Mol Recognit, 17,
513-523.
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T.Shiba,
S.Kametaka,
M.Kawasaki,
M.Shibata,
S.Waguri,
Y.Uchiyama,
and
S.Wakatsuki
(2004).
Insights into the phosphoregulation of beta-secretase sorting signal by the VHS domain of GGA1.
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Traffic, 5,
437-448.
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PDB codes:
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X.P.Huang,
W.P.Chang,
G.Koelsch,
R.T.Turner,
F.Lupu,
and
J.Tang
(2004).
Internalization of exogenously added memapsin 2 (beta-secretase) ectodomain by cells is mediated by amyloid precursor protein.
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J Biol Chem, 279,
37886-37894.
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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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Links
