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PDBsum entry 1bk5
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Protein transport
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PDB id
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1bk5
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Contents |
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* Residue conservation analysis
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DOI no:
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Cell
94:193-204
(1998)
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PubMed id:
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Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin alpha.
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E.Conti,
M.Uy,
L.Leighton,
G.Blobel,
J.Kuriyan.
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ABSTRACT
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Selective nuclear import is mediated by nuclear localization signals (NLSs) and
cognate transport factors known as karyopherins or importins. Karyopherin alpha
recognizes "classical" monopartite and bipartite NLSs. We report the
crystal structure of a 50 kDa fragment of the 60 kDa yeast karyopherin alpha, in
the absence and presence of a monopartite NLS peptide at 2.2 A and 2.8 A
resolution, respectively. The structure shows a tandem array of ten armadillo
repeats, organized in a right-handed superhelix of helices. Binding of the NLS
peptide occurs at two sites within a helical surface groove that is lined by
conserved residues. The structure reveals the determinants of NLS specificity
and suggests a model for the recognition of bipartite NLSs.
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Selected figure(s)
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Figure 2.
Figure 2. Three-Dimensional Structure of Kapα50The molecule
contains ten tandem arm repeats, which are shown in different
colors. With the exception of the first motif, each arm repeat
includes three α helices (H1, H2, and H3). The superhelical
axis of the molecule is vertical. All ribbon diagrams were
generated using RIBBONS ([6]).
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Figure 6.
Figure 6. The Kapα50 Dimer in the Crystals(A) Dimer of
Kapα50 viewed approximately down the local molecular dyad axis,
with the two monomers colored in green and magenta. The arm
repeats are numbered sequentially from the N to the C terminus.
The helices of the tenth arm motifs are labeled. Note that the
first arm repeat lacks the H1 helix.(B) The dimer interactions
between the tenth arm repeat of one monomer (in gray with
relevant residues depicted in magenta) contacting the H3 helices
of the central repeats of the second monomer (in gray with
important residues highlighted in green). All the labeled side
chains are highly conserved. Hydrogen bonding contacts are shown
in dotted lines.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1998,
94,
193-204)
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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A.M.Mehdi,
M.S.Sehgal,
B.Kobe,
T.L.Bailey,
and
M.Bodén
(2011).
A probabilistic model of nuclear import of proteins.
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Bioinformatics,
27,
1239-1246.
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C.F.Lee,
A.V.Hauenstein,
J.K.Fleming,
W.C.Gasper,
V.Engelke,
B.Sankaran,
S.I.Bernstein,
and
T.Huxford
(2011).
X-ray crystal structure of the UCS domain-containing UNC-45 myosin chaperone from Drosophila melanogaster.
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Structure,
19,
397-408.
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PDB code:
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E.Purev,
D.R.Soprano,
and
K.J.Soprano
(2011).
PP2A interaction with Rb2/p130 mediates translocation of Rb2/p130 into the nucleus in all-trans retinoic acid-treated ovarian carcinoma cells.
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J Cell Physiol,
226,
1027-1034.
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R.Webel,
J.Milbradt,
S.Auerochs,
V.Schregel,
C.Held,
K.Nöbauer,
E.Razzazi-Fazeli,
C.Jardin,
T.Wittenberg,
H.Sticht,
and
M.Marschall
(2011).
Two isoforms of the protein kinase pUL97 of human cytomegalovirus are differentially regulated in their nuclear translocation.
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J Gen Virol,
92,
638-649.
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T.L.Yeh,
C.Y.Lee,
L.M.Amzel,
P.J.Espenshade,
and
M.A.Bianchet
(2011).
The hypoxic regulator of sterol synthesis nro1 is a nuclear import adaptor.
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Structure,
19,
503-514.
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PDB code:
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A.Giesecke,
and
M.Stewart
(2010).
Novel binding of the mitotic regulator TPX2 (target protein for xenopus kinesin-like protein 2) to importin-alpha.
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J Biol Chem,
285,
17628-17635.
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PDB code:
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A.Lange,
L.M.McLane,
R.E.Mills,
S.E.Devine,
and
A.H.Corbett
(2010).
Expanding the definition of the classical bipartite nuclear localization signal.
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Traffic,
11,
311-323.
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C.A.Ewens,
P.Kloppsteck,
A.Förster,
X.Zhang,
and
P.S.Freemont
(2010).
Structural and functional implications of phosphorylation and acetylation in the regulation of the AAA+ protein p97.
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Biochem Cell Biol,
88,
41-48.
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C.Kim,
J.Basner,
and
B.Lee
(2010).
Detecting internally symmetric protein structures.
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BMC Bioinformatics,
11,
303.
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D.Liu,
X.Wu,
M.D.Summers,
A.Lee,
K.J.Ryan,
and
S.C.Braunagel
(2010).
Truncated isoforms of Kap60 facilitate trafficking of Heh2 to the nuclear envelope.
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Traffic,
11,
1506-1518.
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G.Merényi,
E.Kónya,
and
B.G.Vértessy
(2010).
Drosophila proteins involved in metabolism of uracil-DNA possess different types of nuclear localization signals.
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FEBS J,
277,
2142-2156.
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J.B.Kelley,
A.M.Talley,
A.Spencer,
D.Gioeli,
and
B.M.Paschal
(2010).
Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors.
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BMC Cell Biol,
11,
63.
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L.K.Lee,
M.A.Ginsburg,
C.Crovace,
M.Donohoe,
and
D.Stock
(2010).
Structure of the torque ring of the flagellar motor and the molecular basis for rotational switching.
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Nature,
466,
996.
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PDB code:
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M.Mossalam,
A.S.Dixon,
and
C.S.Lim
(2010).
Controlling subcellular delivery to optimize therapeutic effect.
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Ther Deliv,
1,
169-193.
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M.Sibrian-Vazquez,
T.J.Jensen,
and
M.G.Vicente
(2010).
Influence of the number and distribution of NLS peptides on the photosensitizing activity of multimeric porphyrin-NLS.
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Org Biomol Chem,
8,
1160-1172.
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N.D.Marchenko,
W.Hanel,
D.Li,
K.Becker,
N.Reich,
and
U.M.Moll
(2010).
Stress-mediated nuclear stabilization of p53 is regulated by ubiquitination and importin-alpha3 binding.
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Cell Death Differ,
17,
255-267.
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N.Gudleski,
J.M.Flanagan,
E.P.Ryan,
M.C.Bewley,
and
L.J.Parent
(2010).
Directionality of nucleocytoplasmic transport of the retroviral gag protein depends on sequential binding of karyopherins and viral RNA.
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Proc Natl Acad Sci U S A,
107,
9358-9363.
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N.Jiménez-Menéndez,
P.Fernández-Millán,
A.Rubio-Cosials,
C.Arnan,
J.Montoya,
H.T.Jacobs,
P.Bernadó,
M.Coll,
I.Usón,
and
M.Solà
(2010).
Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat.
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Nat Struct Mol Biol,
17,
891-893.
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PDB codes:
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N.Noy
(2010).
Between death and survival: retinoic acid in regulation of apoptosis.
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Annu Rev Nutr,
30,
201-217.
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R.Pawłowski,
E.K.Rajakylä,
M.K.Vartiainen,
and
R.Treisman
(2010).
An actin-regulated importin α/β-dependent extended bipartite NLS directs nuclear import of MRTF-A.
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EMBO J,
29,
3448-3458.
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S.V.Burov,
T.V.Yuablokova,
M.Y.Dorosh,
E.V.Krivizyuk,
A.M.Efremov,
and
S.V.Orlov
(2010).
[GnRH analogues containing SV-40 virus T-antigen nuclear localization sequence].
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Bioorg Khim,
36,
630-637.
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T.J.Mosca,
and
T.L.Schwarz
(2010).
Drosophila Importin-α2 is involved in synapse, axon and muscle development.
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PLoS One,
5,
e15223.
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T.M.Gloster,
and
D.J.Vocadlo
(2010).
Mechanism, Structure, and Inhibition of O-GlcNAc Processing Enzymes.
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Curr Signal Transduct Ther,
5,
74-91.
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Y.Gu,
N.Kaplinsky,
M.Bringmann,
A.Cobb,
A.Carroll,
A.Sampathkumar,
T.I.Baskin,
S.Persson,
and
C.R.Somerville
(2010).
Identification of a cellulose synthase-associated protein required for cellulose biosynthesis.
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Proc Natl Acad Sci U S A,
107,
12866-12871.
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A.Lachish-Zalait,
C.K.Lau,
B.Fichtman,
E.Zimmerman,
A.Harel,
M.R.Gaylord,
D.J.Forbes,
and
M.Elbaum
(2009).
Transportin mediates nuclear entry of DNA in vertebrate systems.
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Traffic,
10,
1414-1428.
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A.N.Nguyen Ba,
A.Pogoutse,
N.Provart,
and
A.M.Moses
(2009).
NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction.
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BMC Bioinformatics,
10,
202.
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B.K.Sathyanarayana,
Y.Hahn,
M.S.Patankar,
I.Pastan,
and
B.Lee
(2009).
Mesothelin, Stereocilin, and Otoancorin are predicted to have superhelical structures with ARM-type repeats.
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BMC Struct Biol,
9,
1.
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D.A.Mason,
D.E.Stage,
and
D.S.Goldfarb
(2009).
Evolution of the metazoan-specific importin alpha gene family.
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J Mol Evol,
68,
351-365.
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E.W.Debler,
G.Blobel,
and
A.Hoelz
(2009).
Nuclear transport comes full circle.
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Nat Struct Mol Biol,
16,
457-459.
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F.Cardarelli,
R.Bizzarri,
M.Serresi,
L.Albertazzi,
and
F.Beltram
(2009).
Probing nuclear localization signal-importin alpha binding equilibria in living cells.
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J Biol Chem,
284,
36638-36646.
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F.Yuan,
J.El Hokayem,
W.Zhou,
and
Y.Zhang
(2009).
FANCI protein binds to DNA and interacts with FANCD2 to recognize branched structures.
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J Biol Chem,
284,
24443-24452.
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G.Zhao,
G.Li,
H.Schindelin,
and
W.J.Lennarz
(2009).
An Armadillo motif in Ufd3 interacts with Cdc48 and is involved in ubiquitin homeostasis and protein degradation.
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Proc Natl Acad Sci U S A,
106,
16197-16202.
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PDB code:
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K.E.Süel,
and
Y.M.Chook
(2009).
Kap104p imports the PY-NLS-containing transcription factor Tfg2p into the nucleus.
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J Biol Chem,
284,
15416-15424.
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K.F.Pulliam,
M.B.Fasken,
L.M.McLane,
J.V.Pulliam,
and
A.H.Corbett
(2009).
The Classical Nuclear Localization Signal Receptor, Importin-{alpha}, Is Required for Efficient Transition Through the G1/S Stage of the Cell Cycle in Saccharomyces cerevisiae.
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Genetics,
181,
105-118.
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L.M.McLane,
and
A.H.Corbett
(2009).
Nuclear localization signals and human disease.
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IUBMB Life,
61,
697-706.
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N.Freitas,
and
C.Cunha
(2009).
Mechanisms and signals for the nuclear import of proteins.
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Curr Genomics,
10,
550-557.
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S.A.Adam
(2009).
The nuclear transport machinery in Caenorhabditis elegans: A central role in morphogenesis.
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Semin Cell Dev Biol,
20,
576-581.
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S.Kosugi,
M.Hasebe,
M.Tomita,
and
H.Yanagawa
(2009).
Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs.
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Proc Natl Acad Sci U S A,
106,
10171-10176.
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S.L.Taylor,
N.Frias-Staheli,
A.García-Sastre,
and
C.S.Schmaljohn
(2009).
Hantaan virus nucleocapsid protein binds to importin alpha proteins and inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B.
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J Virol,
83,
1271-1279.
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S.M.Dias,
K.F.Wilson,
K.S.Rojas,
A.L.Ambrosio,
and
R.A.Cerione
(2009).
The molecular basis for the regulation of the cap-binding complex by the importins.
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Nat Struct Mol Biol,
16,
930-937.
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PDB codes:
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S.Maas,
and
W.M.Gommans
(2009).
Identification of a selective nuclear import signal in adenosine deaminases acting on RNA.
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Nucleic Acids Res,
37,
5822-5829.
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Y.An,
C.Y.Chen,
B.Moyer,
P.Rotkiewicz,
M.A.Elsliger,
A.Godzik,
I.A.Wilson,
and
W.E.Balch
(2009).
Structural and functional analysis of the globular head domain of p115 provides insight into membrane tethering.
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J Mol Biol,
391,
26-41.
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PDB codes:
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Y.Shi
(2009).
Assembly and structure of protein phosphatase 2A.
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Sci China C Life Sci,
52,
135-146.
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Y.Shi
(2009).
Serine/threonine phosphatases: mechanism through structure.
|
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Cell,
139,
468-484.
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A.Schulte,
B.Stolp,
A.Schönichen,
O.Pylypenko,
A.Rak,
O.T.Fackler,
and
M.Geyer
(2008).
The human formin FHOD1 contains a bipartite structure of FH3 and GTPase-binding domains required for activation.
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Structure,
16,
1313-1323.
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PDB code:
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C.D.Malone,
K.A.Falkowska,
A.Y.Li,
S.E.Galanti,
R.C.Kanuru,
E.G.LaMont,
K.C.Mazzarella,
A.J.Micev,
M.M.Osman,
N.K.Piotrowski,
J.W.Suszko,
A.C.Timm,
M.M.Xu,
L.Liu,
and
D.L.Chalker
(2008).
Nucleus-specific importin alpha proteins and nucleoporins regulate protein import and nuclear division in the binucleate Tetrahymena thermophila.
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Eukaryot Cell,
7,
1487-1499.
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J.S.Orange,
and
M.J.May
(2008).
Cell penetrating peptide inhibitors of nuclear factor-kappa B.
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Cell Mol Life Sci,
65,
3564-3591.
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K.E.Süel,
H.Gu,
and
Y.M.Chook
(2008).
Modular organization and combinatorial energetics of proline-tyrosine nuclear localization signals.
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PLoS Biol,
6,
e137.
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K.Tahara,
M.Takagi,
M.Ohsugi,
T.Sone,
F.Nishiumi,
K.Maeshima,
Y.Horiuchi,
N.Tokai-Nishizumi,
F.Imamoto,
T.Yamamoto,
S.Kose,
and
N.Imamoto
(2008).
Importin-beta and the small guanosine triphosphatase Ran mediate chromosome loading of the human chromokinesin Kid.
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J Cell Biol,
180,
493-506.
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L.M.McLane,
K.F.Pulliam,
S.E.Devine,
and
A.H.Corbett
(2008).
The Ty1 integrase protein can exploit the classical nuclear protein import machinery for entry into the nucleus.
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Nucleic Acids Res,
36,
4317-4326.
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M.Hatayama,
T.Tomizawa,
K.Sakai-Kato,
P.Bouvagnet,
S.Kose,
N.Imamoto,
S.Yokoyama,
N.Utsunomiya-Tate,
K.Mikoshiba,
T.Kigawa,
and
J.Aruga
(2008).
Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain.
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Hum Mol Genet,
17,
3459-3473.
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PDB code:
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M.M.Pradeepa,
S.Manjunatha,
V.Sathish,
S.Agrawal,
and
M.R.Rao
(2008).
Involvement of importin-4 in the transport of transition protein 2 into the spermatid nucleus.
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Mol Cell Biol,
28,
4331-4341.
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P.L.Yeung,
L.Y.Chen,
S.C.Tsai,
A.Zhang,
and
J.D.Chen
(2008).
Daxx contains two nuclear localization signals and interacts with importin alpha3.
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J Cell Biochem,
103,
456-470.
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Q.Li,
N.Zhang,
D.Zhang,
Y.Wang,
T.Lin,
Y.Wang,
H.Zhou,
Z.Ye,
F.Zhang,
S.C.Lin,
and
J.Han
(2008).
Determinants that control the distinct subcellular localization of p38alpha-PRAK and p38beta-PRAK complexes.
|
| |
J Biol Chem,
283,
11014-11023.
|
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S.S.Haenni,
M.Altmeyer,
P.O.Hassa,
T.Valovka,
M.Fey,
and
M.O.Hottiger
(2008).
Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS.
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BMC Cell Biol,
9,
39.
|
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W.Chen,
S.S.Lam,
H.Srinath,
Z.Jiang,
J.J.Correia,
C.A.Schiffer,
K.A.Fitzgerald,
K.Lin,
and
W.E.Royer
(2008).
Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5.
|
| |
Nat Struct Mol Biol,
15,
1213-1220.
|
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PDB code:
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|
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A.Cook,
F.Bono,
M.Jinek,
and
E.Conti
(2007).
Structural biology of nucleocytoplasmic transport.
|
| |
Annu Rev Biochem,
76,
647-671.
|
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|
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A.Lange,
R.E.Mills,
C.J.Lange,
M.Stewart,
S.E.Devine,
and
A.H.Corbett
(2007).
Classical nuclear localization signals: definition, function, and interaction with importin alpha.
|
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PDB code:
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PDB code:
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PDB code:
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PDB code:
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PDB code:
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PDB code:
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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
code is
shown on the right.
|
');
}
}
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