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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Transport/nuclear protein
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Title:
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Gdpran-ntf2 complex
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Structure:
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Nuclear transport factor 2. Chain: a, b. Synonym: ntf2, p10, pp15. Engineered: yes. Ran. Chain: c, d, e. Synonym: gsp1p, tc4. Engineered: yes
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Source:
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Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell_line: bl21. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Canis lupus familiaris. Dog. Organism_taxid: 9615.
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Biol. unit:
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Pentamer (from
)
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Resolution:
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2.50Å
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R-factor:
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0.215
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R-free:
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0.273
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Authors:
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M.Stewart,H.M.Kent,A.J.Mccoy
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Key ref:
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M.Stewart
et al.
(1998).
Structural basis for molecular recognition between nuclear transport factor 2 (NTF2) and the GDP-bound form of the Ras-family GTPase Ran.
J Mol Biol,
277,
635-646.
PubMed id:
DOI:
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Date:
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06-Jan-98
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Release date:
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29-Apr-98
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PROCHECK
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Headers
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References
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DOI no:
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J Mol Biol
277:635-646
(1998)
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PubMed id:
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Structural basis for molecular recognition between nuclear transport factor 2 (NTF2) and the GDP-bound form of the Ras-family GTPase Ran.
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M.Stewart,
H.M.Kent,
A.J.McCoy.
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ABSTRACT
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Nuclear transport factor 2 (NTF2) and the Ras-family GTPase Ran are two soluble
components of the nuclear protein import machinery. NTF2 binds GDP-Ran
selectively and this interaction is important for efficient nuclear protein
import in vivo. We have used X-ray crystallography to determine the structure of
the macromolecular complex formed between GDP-Ran and nuclear transport factor 2
(NTF2) at 2.5 A resolution. The interaction interface involves primarily the
putative switch II loop of Ran (residues 65 to 78) and the hydrophobic cavity
and surrounding surface of NTF2. The major contribution to the interaction made
by the switch II loop accounts for the ability of NTF2 to discriminate between
GDP and GTP-bound forms of Ran. The aromatic side-chain of Ran Phe72 inserts
into the NTF2 cavity and accounts for 22% of the surface area buried by the
interaction interface, while salt bridges are formed between Lys71 and Arg76 of
Ran with Asp92/Asp94 and Glu42 of NTF2, respectively. These salt bridges account
for the inhibition of the Ran-NTF2 interaction by NTF2 mutants such as E42 K and
D92/94N in which the negatively charged residues surrounding the cavity were
altered. Because the interaction interface maintains the positions of key Ran
residues involved in binding MgGDP, NTF2 binding may help stabilize the switch
state of Ran, possibly in the context of targeting it to other components of the
nuclear protein import machinery to specify directionality of transport. The
binding of GDP-Ran at the NTF2 cavity raises the possibility that this
interaction might be modulated by a metabolite or small molecule substrate for
NTF2's putative enzymatic activity.
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Selected figure(s)
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Figure 4.
Figure 4. Stereo view showing the arrangement of residues
contributing to the molecular surface at the top of the
hydrophobic cavity of NTF2 (shown as a stick model) and the
aromatic ring of Ran Phe72 (shown as a CPK model) in the
complex. The ring of Ran Phe72 is lodged in the cavity
surrounded by the hydrophobic side-chains of NTF2 Trp41, Leu59,
Phe61, Ile64, Leu89, Ala91, Met97, Phe119 and Leu121. The
remainder of the switch II region of GDP-Ran and its interaction
interface with NTF2 is illustrated in Figure 5.
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Figure 6.
Figure 6. Schematic illustration showing key features of
the interface between NTF2 and GDP-Ran. The switch II loop of
Ran interfaces primarily with residues that contribute to the
molecular surface of the upper portion of the hydrophobic cavity
of NTF2 and also with negatively charged residues (Glu42,
Asp92 and Asp94) that surround the entrance to the cavity. The
switch I loop of Ran interacts with the NTF2 C terminus (Leu123,
His124 and Asn125) that is poorly ordered in NTF2 crystals
[Bullock et al 1996].
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
277,
635-646)
copyright 1998.
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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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C.Bian,
Q.Ruan,
Z.Peng,
H.Ji,
L.Jiang,
J.Li,
and
L.Yuan
(2011).
Cloning, expression and characterization of the putative nuclear transport factor 2 (NTF2) gene from moss Conocephalum conicum(L.) Dum.
|
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Mol Biol Rep,
38,
2023-2032.
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L.J.Colwell,
M.P.Brenner,
and
K.Ribbeck
(2010).
Charge as a selection criterion for translocation through the nuclear pore complex.
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PLoS Comput Biol,
6,
e1000747.
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|
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J.R.Partridge,
and
T.U.Schwartz
(2009).
Crystallographic and biochemical analysis of the Ran-binding zinc finger domain.
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J Mol Biol,
391,
375-389.
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PDB codes:
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K.Lui,
and
Y.Huang
(2009).
RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking.
|
| |
Mol Cell Pharmacol,
1,
148-156.
|
|
|
|
|
|
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L.Miao,
and
K.Schulten
(2009).
Transport-related structures and processes of the nuclear pore complex studied through molecular dynamics.
|
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Structure,
17,
449-459.
|
|
|
|
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|
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R.Peters
(2009).
Translocation through the nuclear pore: Kaps pave the way.
|
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Bioessays,
31,
466-477.
|
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|
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K.Van Impe,
T.Hubert,
V.De Corte,
B.Vanloo,
C.Boucherie,
J.Vandekerckhove,
and
J.Gettemans
(2008).
A new role for nuclear transport factor 2 and Ran: nuclear import of CapG.
|
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Traffic,
9,
695-707.
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|
|
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A.Cook,
F.Bono,
M.Jinek,
and
E.Conti
(2007).
Structural biology of nucleocytoplasmic transport.
|
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Annu Rev Biochem,
76,
647-671.
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|
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A.Paradise,
M.K.Levin,
G.Korza,
and
J.H.Carson
(2007).
Significant proportions of nuclear transport proteins with reduced intracellular mobilities resolved by fluorescence correlation spectroscopy.
|
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J Mol Biol,
365,
50-65.
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|
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|
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A.V.Sorokin,
E.R.Kim,
and
L.P.Ovchinnikov
(2007).
Nucleocytoplasmic transport of proteins.
|
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Biochemistry (Mosc),
72,
1439-1457.
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|
|
|
|
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K.Li,
B.Ossareh-Nazari,
X.Liu,
C.Dargemont,
and
R.Marmorstein
(2007).
Molecular basis for bre5 cofactor recognition by the ubp3 deubiquitylating enzyme.
|
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J Mol Biol,
372,
194-204.
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PDB code:
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M.Stewart
(2007).
Molecular mechanism of the nuclear protein import cycle.
|
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Nat Rev Mol Cell Biol,
8,
195-208.
|
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|
|
|
|
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N.Handa,
S.Kishishita,
S.Morita,
R.Akasaka,
Z.Jin,
J.Chrzas,
L.Chen,
Z.J.Liu,
B.C.Wang,
S.Sugano,
A.Tanaka,
T.Terada,
M.Shirouzu,
and
S.Yokoyama
(2007).
Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form.
|
| |
Acta Crystallogr D Biol Crystallogr,
63,
1225-1234.
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PDB code:
|
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W.Yao,
D.Roser,
A.Köhler,
B.Bradatsch,
J.Bassler,
and
E.Hurt
(2007).
Nuclear export of ribosomal 60S subunits by the general mRNA export receptor Mex67-Mtr2.
|
| |
Mol Cell,
26,
51-62.
|
|
|
|
|
|
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A.S.Madrid,
and
K.Weis
(2006).
Nuclear transport is becoming crystal clear.
|
| |
Chromosoma,
115,
98.
|
|
|
|
|
|
|
S.Bailey,
D.Ward,
R.Middleton,
J.G.Grossmann,
and
P.C.Zambryski
(2006).
Agrobacterium tumefaciens VirB8 structure reveals potential protein-protein interaction sites.
|
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Proc Natl Acad Sci U S A,
103,
2582-2587.
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PDB code:
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K.Li,
K.Zhao,
B.Ossareh-Nazari,
G.Da,
C.Dargemont,
and
R.Marmorstein
(2005).
Structural basis for interaction between the Ubp3 deubiquitinating enzyme and its Bre5 cofactor.
|
| |
J Biol Chem,
280,
29176-29185.
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PDB code:
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L.F.Pemberton,
and
B.M.Paschal
(2005).
Mechanisms of receptor-mediated nuclear import and nuclear export.
|
| |
Traffic,
6,
187-198.
|
|
|
|
|
|
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L.Terradot,
R.Bayliss,
C.Oomen,
G.A.Leonard,
C.Baron,
and
G.Waksman
(2005).
Structures of two core subunits of the bacterial type IV secretion system, VirB8 from Brucella suis and ComB10 from Helicobacter pylori.
|
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Proc Natl Acad Sci U S A,
102,
4596-4601.
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PDB codes:
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U.Kubitscheck,
D.Grünwald,
A.Hoekstra,
D.Rohleder,
T.Kues,
J.P.Siebrasse,
and
R.Peters
(2005).
Nuclear transport of single molecules: dwell times at the nuclear pore complex.
|
| |
J Cell Biol,
168,
233-243.
|
|
|
|
|
|
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M.Yamada,
I.W.Mattaj,
and
Y.Yoneda
(2004).
An ATP-dependent activity that releases RanGDP from NTF2.
|
| |
J Biol Chem,
279,
36228-36234.
|
|
|
|
|
|
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A.F.Neuwald,
N.Kannan,
A.Poleksic,
N.Hata,
and
J.S.Liu
(2003).
Ran's C-terminal, basic patch, and nucleotide exchange mechanisms in light of a canonical structure for Rab, Rho, Ras, and Ran GTPases.
|
| |
Genome Res,
13,
673-692.
|
|
|
|
|
|
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C.A.Kerfeld,
M.R.Sawaya,
V.Brahmandam,
D.Cascio,
K.K.Ho,
C.C.Trevithick-Sutton,
D.W.Krogmann,
and
T.O.Yeates
(2003).
The crystal structure of a cyanobacterial water-soluble carotenoid binding protein.
|
| |
Structure,
11,
55-65.
|
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PDB code:
|
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|
|
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C.Senay,
P.Ferrari,
C.Rocher,
K.J.Rieger,
J.Winter,
D.Platel,
and
Y.Bourne
(2003).
The Mtr2-Mex67 NTF2-like domain complex. Structural insights into a dual role of Mtr2 for yeast nuclear export.
|
| |
J Biol Chem,
278,
48395-48403.
|
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PDB codes:
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M.Weichel,
P.Schmid-Grendelmeier,
S.Flückiger,
M.Breitenbach,
K.Blaser,
and
R.Crameri
(2003).
Nuclear transport factor 2 represents a novel cross-reactive fungal allergen.
|
| |
Allergy,
58,
198-206.
|
|
|
|
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|
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N.I.Kiskin,
J.P.Siebrasse,
and
R.Peters
(2003).
Optical microwell assay of membrane transport kinetics.
|
| |
Biophys J,
85,
2311-2322.
|
|
|
|
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|
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R.Nevo,
C.Stroh,
F.Kienberger,
D.Kaftan,
V.Brumfeld,
M.Elbaum,
Z.Reich,
and
P.Hinterdorfer
(2003).
A molecular switch between alternative conformational states in the complex of Ran and importin beta1.
|
| |
Nat Struct Biol,
10,
553-557.
|
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|
|
|
|
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A.E.Todd,
C.A.Orengo,
and
J.M.Thornton
(2002).
Sequence and structural differences between enzyme and nonenzyme homologs.
|
| |
Structure,
10,
1435-1451.
|
|
|
|
|
|
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I.C.Braun,
A.Herold,
M.Rode,
and
E.Izaurralde
(2002).
Nuclear export of mRNA by TAP/NXF1 requires two nucleoporin-binding sites but not p15.
|
| |
Mol Cell Biol,
22,
5405-5418.
|
|
|
|
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|
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K.Plafker,
and
I.G.Macara
(2002).
Fluorescence resonance energy transfer biosensors that detect Ran conformational changes and a Ran x GDP-importin-beta -RanBP1 complex in vitro and in intact cells.
|
| |
J Biol Chem,
277,
30121-30127.
|
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|
|
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|
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R.Bayliss,
S.W.Leung,
R.P.Baker,
B.B.Quimby,
A.H.Corbett,
and
M.Stewart
(2002).
Structural basis for the interaction between NTF2 and nucleoporin FxFG repeats.
|
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EMBO J,
21,
2843-2853.
|
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PDB codes:
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R.Bayliss,
T.Littlewood,
L.A.Strawn,
S.R.Wente,
and
M.Stewart
(2002).
GLFG and FxFG nucleoporins bind to overlapping sites on importin-beta.
|
| |
J Biol Chem,
277,
50597-50606.
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PDB codes:
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B.B.Quimby,
S.W.Leung,
R.Bayliss,
M.T.Harreman,
G.Thirumala,
M.Stewart,
and
A.H.Corbett
(2001).
Functional analysis of the hydrophobic patch on nuclear transport factor 2 involved in interactions with the nuclear pore in vivo.
|
| |
J Biol Chem,
276,
38820-38829.
|
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E.Conti,
and
E.Izaurralde
(2001).
Nucleocytoplasmic transport enters the atomic age.
|
| |
Curr Opin Cell Biol,
13,
310-319.
|
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|
|
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|
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I.G.Macara
(2001).
Transport into and out of the nucleus.
|
| |
Microbiol Mol Biol Rev,
65,
570.
|
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|
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|
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I.R.Vetter,
and
A.Wittinghofer
(2001).
The guanine nucleotide-binding switch in three dimensions.
|
| |
Science,
294,
1299-1304.
|
|
|
|
|
|
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K.D.Corbett,
and
T.Alber
(2001).
The many faces of Ras: recognition of small GTP-binding proteins.
|
| |
Trends Biochem Sci,
26,
710-716.
|
|
|
|
|
|
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K.Ribbeck,
and
D.Görlich
(2001).
Kinetic analysis of translocation through nuclear pore complexes.
|
| |
EMBO J,
20,
1320-1330.
|
|
|
|
|
|
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L.Renault,
J.Kuhlmann,
A.Henkel,
and
A.Wittinghofer
(2001).
Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1).
|
| |
Cell,
105,
245-255.
|
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PDB code:
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|
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S.Fribourg,
I.C.Braun,
E.Izaurralde,
and
E.Conti
(2001).
Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor.
|
| |
Mol Cell,
8,
645-656.
|
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PDB codes:
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S.Padmanabhan,
and
D.M.Freymann
(2001).
The conformation of bound GMPPNP suggests a mechanism for gating the active site of the SRP GTPase.
|
| |
Structure,
9,
859-867.
|
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PDB codes:
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B.B.Quimby,
C.A.Wilson,
and
A.H.Corbett
(2000).
The interaction between Ran and NTF2 is required for cell cycle progression.
|
| |
Mol Biol Cell,
11,
2617-2629.
|
|
|
|
|
|
|
C.Chaillan-Huntington,
C.V.Braslavsky,
J.Kuhlmann,
and
M.Stewart
(2000).
Dissecting the interactions between NTF2, RanGDP, and the nucleoporin XFXFG repeats.
|
| |
J Biol Chem,
275,
5874-5879.
|
|
|
|
|
|
|
C.M.Lane,
I.Cushman,
and
M.S.Moore
(2000).
Selective disruption of nuclear import by a functional mutant nuclear transport carrier.
|
| |
J Cell Biol,
151,
321-332.
|
|
|
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|
|
|
M.Stewart
(2000).
Insights into the molecular mechanism of nuclear trafficking using nuclear transport factor 2 (NTF2).
|
| |
Cell Struct Funct,
25,
217-225.
|
|
|
|
|
|
|
R.P.Baker,
and
M.Stewart
(2000).
Crystallization and preliminary X-ray diffraction analysis of the Saccharomyces cerevisiae ran-binding protein Mog1p.
|
| |
Acta Crystallogr D Biol Crystallogr,
56,
229-231.
|
|
|
|
|
|
|
S.M.Steggerda,
B.E.Black,
and
B.M.Paschal
(2000).
Monoclonal antibodies to NTF2 inhibit nuclear protein import by preventing nuclear translocation of the GTPase Ran.
|
| |
Mol Biol Cell,
11,
703-719.
|
|
|
|
|
|
|
T.Nishimoto
(2000).
Upstream and downstream of ran GTPase.
|
| |
Biol Chem,
381,
397-405.
|
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|
|
|
Y.Azuma,
and
M.Dasso
(2000).
The role of Ran in nuclear function.
|
| |
Curr Opin Cell Biol,
12,
302-307.
|
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A.E.Nixon,
S.M.Firestine,
F.G.Salinas,
and
S.J.Benkovic
(1999).
Rational design of a scytalone dehydratase-like enzyme using a structurally homologous protein scaffold.
|
| |
Proc Natl Acad Sci U S A,
96,
3568-3571.
|
|
|
|
|
|
|
B.E.Black,
L.Lévesque,
J.M.Holaska,
T.C.Wood,
and
B.M.Paschal
(1999).
Identification of an NTF2-related factor that binds Ran-GTP and regulates nuclear protein export.
|
| |
Mol Cell Biol,
19,
8616-8624.
|
|
|
|
|
|
|
D.Görlich,
and
U.Kutay
(1999).
Transport between the cell nucleus and the cytoplasm.
|
| |
Annu Rev Cell Dev Biol,
15,
607-660.
|
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|
|
|
|
|
I.R.Vetter,
A.Arndt,
U.Kutay,
D.Görlich,
and
A.Wittinghofer
(1999).
Structural view of the Ran-Importin beta interaction at 2.3 A resolution.
|
| |
Cell,
97,
635-646.
|
|
|
PDB code:
|
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|
|
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|
|
J.Katahira,
K.Strässer,
A.Podtelejnikov,
M.Mann,
J.U.Jung,
and
E.Hurt
(1999).
The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human.
|
| |
EMBO J,
18,
2593-2609.
|
|
|
|
|
|
|
M.Floer,
and
G.Blobel
(1999).
Putative reaction intermediates in Crm1-mediated nuclear protein export.
|
| |
J Biol Chem,
274,
16279-16286.
|
|
|
|
|
|
|
S.J.Gamblin,
and
S.J.Smerdon
(1999).
Nuclear transport: what a kary-on!
|
| |
Structure,
7,
R199-R204.
|
|
|
|
|
|
|
W.Hu,
and
D.A.Jans
(1999).
Efficiency of importin alpha/beta-mediated nuclear localization sequence recognition and nuclear import. Differential role of NTF2.
|
| |
J Biol Chem,
274,
15820-15827.
|
|
|
|
|
|
|
Y.M.Chook,
G.Cingolani,
E.Conti,
M.Stewart,
I.Vetter,
and
A.Wittinghofer
(1999).
Pictures in cell biology. Structures of nuclear-transport components.
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K.Ribbeck,
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M.Stewart,
and
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NTF2 mediates nuclear import of Ran.
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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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