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PDBsum entry 2pfv
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Endocytosis/exocytosis
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PDB id
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2pfv
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Contents |
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* Residue conservation analysis
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DOI no:
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J Mol Biol
371:410-421
(2007)
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PubMed id:
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The crystal structure of mouse Exo70 reveals unique features of the mammalian exocyst.
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B.A.Moore,
H.H.Robinson,
Z.Xu.
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ABSTRACT
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The exocyst is a eukaryotic tethering complex necessary for the fusion of
exocytic vesicles with the plasma membrane. Its function in vivo is tightly
regulated by interactions with multiple small GTPases. Exo70, one of the eight
subunits of the exocyst, is important for the localization of the exocyst to the
plasma membrane. It interacts with TC10 and Rho3 GTPases in mammals and yeast,
respectively, and has been shown recently to bind to the actin-polymerization
complex Arp2/3. Here, we present the crystal structure of Mus musculus Exo70 at
2.25 A resolution. Exo70 is composed of alpha-helices in a series of
right-handed helix-turn-helix motifs organized into a long rod of length 170 A
and width 35 A. Although the alpha-helical organization of this molecule is
similar to that in Saccharomyces cerevisiae Exo70, major structural differences
are observed on the surface of the molecule, at the domain boundaries, and in
various loop structures. In particular, the C-terminal domain of M. musculus
Exo70 adopts a new orientation relative to the N-terminal half not seen in S.
cerevisiae Exo70 structures. Given the low level of sequence conservation within
Exo70, this structure provides new insights into our understanding of many
species-specific functions of the exocyst.
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Selected figure(s)
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Figure 1.
Figure 1. A stereo cartoon diagram of MmExo70 is shown.
Residues are shown in color: N domain, red; M domain, yellow;
and C domain, blue. The α-helices are drawn as coils and
labeled from H1 to H19; turns and loops, solid tubes; unobserved
residues, broken lines (no β strands are observed in the
structure).
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Figure 2.
Figure 2. Structural alignment of Exo70 in M. musculus, H.
sapiens, D. melanogaster, S. pombe, and S. cerevisiae. Invariant
residues are shaded purple. Similar but not identical residues
are shaded pink. Secondary structural elements are indicated
above the sequence block for MmExo70 and below for ScExo70:
α-helices, rectangles; other elements, continuous lines;
structurally unobserved residues, broken lines. For MmExo70: N
domain, red; M domain, yellow; and C domain, blue (same as
Figure 1). For ScExo70: N domain, brown; M domain, green; and C
domain, cyan. For clarity, sequences lacking homology or
unobserved in the structures have been replaced with bracketed
numbers indicating the number of residues omitted.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
371,
410-421)
copyright 2007.
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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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M.Hertzog,
and
P.Chavrier
(2011).
Cell polarity during motile processes: keeping on track with the exocyst complex.
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Biochem J,
433,
403-409.
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S.Ory,
and
S.Gasman
(2011).
Rho GTPases and exocytosis: what are the molecular links?
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Semin Cell Dev Biol,
22,
27-32.
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F.J.Pérez-Victoria,
G.Abascal-Palacios,
I.Tascón,
A.Kajava,
J.G.Magadán,
E.P.Pioro,
J.S.Bonifacino,
and
A.Hierro
(2010).
Structural basis for the wobbler mouse neurodegenerative disorder caused by mutation in the Vps54 subunit of the GARP complex.
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Proc Natl Acad Sci U S A,
107,
12860-12865.
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PDB codes:
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H.Wu,
C.Turner,
J.Gardner,
B.Temple,
and
P.Brennwald
(2010).
The Exo70 subunit of the exocyst is an effector for both Cdc42 and Rho3 function in polarized exocytosis.
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Mol Biol Cell,
21,
430-442.
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I.M.Yu,
and
F.M.Hughson
(2010).
Tethering factors as organizers of intracellular vesicular traffic.
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Annu Rev Cell Dev Biol,
26,
137-156.
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K.Baek,
A.Knödler,
S.H.Lee,
X.Zhang,
K.Orlando,
J.Zhang,
T.J.Foskett,
W.Guo,
and
R.Dominguez
(2010).
Structure-function study of the N-terminal domain of exocyst subunit Sec3.
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J Biol Chem,
285,
10424-10433.
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PDB code:
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M.Yamashita,
K.Kurokawa,
Y.Sato,
A.Yamagata,
H.Mimura,
A.Yoshikawa,
K.Sato,
A.Nakano,
and
S.Fukai
(2010).
Structural basis for the Rho- and phosphoinositide-dependent localization of the exocyst subunit Sec3.
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Nat Struct Mol Biol,
17,
180-186.
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PDB code:
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A.H.Hutagalung,
J.Coleman,
M.Pypaert,
and
P.J.Novick
(2009).
An internal domain of Exo70p is required for actin-independent localization and mediates assembly of specific exocyst components.
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Mol Biol Cell,
20,
153-163.
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A.Tripathi,
Y.Ren,
P.D.Jeffrey,
and
F.M.Hughson
(2009).
Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complex.
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Nat Struct Mol Biol,
16,
114-123.
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PDB codes:
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B.C.Richardson,
R.D.Smith,
D.Ungar,
A.Nakamura,
P.D.Jeffrey,
V.V.Lupashin,
and
F.M.Hughson
(2009).
Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.
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Proc Natl Acad Sci U S A,
106,
13329-13334.
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PDB code:
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B.He,
and
W.Guo
(2009).
The exocyst complex in polarized exocytosis.
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Curr Opin Cell Biol,
21,
537-542.
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E.Sztul,
and
V.Lupashin
(2009).
Role of vesicle tethering factors in the ER-Golgi membrane traffic.
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FEBS Lett,
583,
3770-3783.
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H.Lu,
L.Lin,
S.Sato,
Y.Xing,
and
C.J.Lee
(2009).
Predicting functional alternative splicing by measuring RNA selection pressure from multigenome alignments.
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PLoS Comput Biol,
5,
e1000608.
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J.A.Songer,
and
M.Munson
(2009).
Sec6p anchors the assembled exocyst complex at sites of secretion.
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Mol Biol Cell,
20,
973-982.
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N.J.Croteau,
M.L.Furgason,
D.Devos,
and
M.Munson
(2009).
Conservation of helical bundle structure between the exocyst subunits.
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PLoS ONE,
4,
e4443.
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T.Hubert,
J.Vandekerckhove,
and
J.Gettemans
(2009).
Exo70-mediated recruitment of nucleoporin Nup62 at the leading edge of migrating cells is required for cell migration.
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Traffic,
10,
1257-1271.
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Y.Ren,
C.K.Yip,
A.Tripathi,
D.Huie,
P.D.Jeffrey,
T.Walz,
and
F.M.Hughson
(2009).
A structure-based mechanism for vesicle capture by the multisubunit tethering complex Dsl1.
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Cell,
139,
1119-1129.
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PDB code:
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T.Saito,
T.Shibasaki,
and
S.Seino
(2008).
Involvement of Exoc3l, a protein structurally related to the exocyst subunit Sec6, in insulin secretion.
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Biomed Res,
29,
85-91.
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J.Liu,
X.Zuo,
P.Yue,
and
W.Guo
(2007).
Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells.
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Mol Biol Cell,
18,
4483-4492.
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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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