|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Protein binding
|
|
|
Title:
|
|
Crystal structure of the zink-knuckle 2 domain of human clip-170 in complex with cap-gly domain of human dynactin-1 (p150-glued)
|
|
Structure:
|
|
Dynactin subunit 1. Chain: a, b, c, d. Fragment: cap-gly domain. Synonym: 150 kda dynein-associated polypeptide, dap-150, dp-150, p150-glued, p135. Engineered: yes. Cap-gly domain-containing linker protein 1. Chain: e, f, g, h. Fragment: zn-knuckle 2.
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: dctn1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: clip1, cyln1, rsn.
|
|
Resolution:
|
|
|
2.60Å
|
R-factor:
|
0.193
|
R-free:
|
0.238
|
|
|
Authors:
|
|
A.Weisbrich,S.Honnappa,G.Capitani,M.O.Steinmetz
|
Key ref:
|
|
A.Weisbrich
et al.
(2007).
Structure-function relationship of CAP-Gly domains.
Nat Struct Biol,
14,
959-967.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
06-Aug-08
|
Release date:
|
19-Aug-08
|
|
|
Supersedes:
|
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q14203
(DCTN1_HUMAN) -
Dynactin subunit 1 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
1278 a.a.
71 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
Chains A, B, C, D, E, F, G, H:
E.C.?
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Nat Struct Biol
14:959-967
(2007)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure-function relationship of CAP-Gly domains.
|
|
A.Weisbrich,
S.Honnappa,
R.Jaussi,
O.Okhrimenko,
D.Frey,
I.Jelesarov,
A.Akhmanova,
M.O.Steinmetz.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
In all eukaryotes, CAP-Gly proteins control important cellular processes. The
molecular mechanisms underlying the functions of CAP-Gly domains, however, are
still poorly understood. Here we use the complex formed between the CAP-Gly
domain of p150(glued) and the C-terminal zinc knuckle of CLIP170 as a model
system to explore the structure-function relationship of CAP-Gly-mediated
protein interactions. We demonstrate that the conserved GKNDG motif of CAP-Gly
domains is responsible for targeting to the C-terminal EEY/F sequence motifs of
CLIP170, EB proteins and microtubules. The CAP-Gly-EEY/F interaction is
essential for the recruitment of the dynactin complex by CLIP170 and for
activation of CLIP170. Our findings define the molecular basis of CAP-Gly domain
function, including the tubulin detyrosination-tyrosination cycle. They further
establish fundamental roles for the interaction between CAP-Gly proteins and
C-terminal EEY/F sequence motifs in regulating complex and dynamic cellular
processes.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 4.
(a–e) COS-7 cells were transfected with constructs
expressing YFP or the indicated fluorescent CLIP170 fusions and
stained for endogenous p150^glued. Schematic representations of
CLIP170 fusions are shown at left; CAP-Gly domains (CG1, CG2),
zinc knuckles (Zn1, Zn2), DDETF motif and coiled-coil region are
indicated. Right images show overlays of YFP fluorescence
(green) and staining of endogenous p150^glued (magenta). Inset
in the middle panel in a shows an enlargement of the boxed area
to illustrate localization of p150^glued to microtubule tips in
control cells. Bar, 10  m.
|
|
Figure 7.
Olive, orange and blue double arrows represent interactions
mediated by CLIP170 CAP-Gly, p150^glued CAP-Gly and the
calponin-homology (CH) domain of EB1, respectively. Dashed and
solid lines denote intra- and intermolecular interactions,
respectively. Note that EB1, CLIP170 and p150^glued form
parallel dimers; however, for simplicity only the monomers are
depicted.
|
|
|
|
|
|
| |
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
959-967)
copyright 2007.
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
A.Szyk,
A.M.Deaconescu,
G.Piszczek,
and
A.Roll-Mecak
(2011).
Tubulin tyrosine ligase structure reveals adaptation of an ancient fold to bind and modify tubulin.
|
| |
Nat Struct Mol Biol,
18,
1250-1258.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
T.M.Huckaba,
A.Gennerich,
J.E.Wilhelm,
A.H.Chishti,
and
R.D.Vale
(2011).
Kinesin-73 Is a Processive Motor That Localizes to Rab5-containing Organelles.
|
| |
J Biol Chem,
286,
7457-7467.
|
|
|
|
|
|
|
C.Janke,
and
M.Kneussel
(2010).
Tubulin post-translational modifications: encoding functions on the neuronal microtubule cytoskeleton.
|
| |
Trends Neurosci,
33,
362-372.
|
|
|
|
|
|
|
C.M.Gould,
F.Diella,
A.Via,
P.Puntervoll,
C.Gemünd,
S.Chabanis-Davidson,
S.Michael,
A.Sayadi,
J.C.Bryne,
C.Chica,
M.Seiler,
N.E.Davey,
N.Haslam,
R.J.Weatheritt,
A.Budd,
T.Hughes,
J.Pas,
L.Rychlewski,
G.Travé,
R.Aasland,
M.Helmer-Citterich,
R.Linding,
and
T.J.Gibson
(2010).
ELM: the status of the 2010 eukaryotic linear motif resource.
|
| |
Nucleic Acids Res,
38,
D167-D180.
|
|
|
|
|
|
|
C.O.De Groot,
I.Jelesarov,
F.F.Damberger,
S.Bjelić,
M.A.Schärer,
N.S.Bhavesh,
I.Grigoriev,
R.M.Buey,
K.Wüthrich,
G.Capitani,
A.Akhmanova,
and
M.O.Steinmetz
(2010).
Molecular insights into mammalian end-binding protein heterodimerization.
|
| |
J Biol Chem,
285,
5802-5814.
|
|
|
|
|
|
|
C.Wider,
J.C.Dachsel,
M.J.Farrer,
D.W.Dickson,
Y.Tsuboi,
and
Z.K.Wszolek
(2010).
Elucidating the genetics and pathology of Perry syndrome.
|
| |
J Neurol Sci,
289,
149-154.
|
|
|
|
|
|
|
H.Jo,
F.Loison,
H.Hattori,
L.E.Silberstein,
H.Yu,
and
H.R.Luo
(2010).
Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs.
|
| |
PLoS One,
5,
e10318.
|
|
|
|
|
|
|
H.S.Lee,
Y.A.Komarova,
E.S.Nadezhdina,
R.Anjum,
J.G.Peloquin,
J.M.Schober,
O.Danciu,
J.van Haren,
N.Galjart,
S.P.Gygi,
A.Akhmanova,
and
G.G.Borisy
(2010).
Phosphorylation controls autoinhibition of cytoplasmic linker protein-170.
|
| |
Mol Biol Cell,
21,
2661-2673.
|
|
|
|
|
|
|
K.A.Blake-Hodek,
L.Cassimeris,
and
T.C.Huffaker
(2010).
Regulation of microtubule dynamics by Bim1 and Bik1, the budding yeast members of the EB1 and CLIP-170 families of plus-end tracking proteins.
|
| |
Mol Biol Cell,
21,
2013-2023.
|
|
|
|
|
|
|
K.K.Gupta,
M.V.Joyce,
A.R.Slabbekoorn,
Z.C.Zhu,
B.A.Paulson,
B.Boggess,
and
H.V.Goodson
(2010).
Probing interactions between CLIP-170, EB1, and microtubules.
|
| |
J Mol Biol,
395,
1049-1062.
|
|
|
|
|
|
|
N.Galjart
(2010).
Plus-end-tracking proteins and their interactions at microtubule ends.
|
| |
Curr Biol,
20,
R528-R537.
|
|
|
|
|
|
|
S.B.Skube,
J.M.Chaverri,
and
H.V.Goodson
(2010).
Effect of GFP tags on the localization of EB1 and EB1 fragments in vivo.
|
| |
Cytoskeleton (Hoboken),
67,
1.
|
|
|
|
|
|
|
A.J.Lomakin,
I.Semenova,
I.Zaliapin,
P.Kraikivski,
E.Nadezhdina,
B.M.Slepchenko,
A.Akhmanova,
and
V.Rodionov
(2009).
CLIP-170-dependent capture of membrane organelles by microtubules initiates minus-end directed transport.
|
| |
Dev Cell,
17,
323-333.
|
|
|
|
|
|
|
C.Vilariño-Güell,
C.Wider,
A.I.Soto-Ortolaza,
S.A.Cobb,
J.M.Kachergus,
B.H.Keeling,
J.C.Dachsel,
M.M.Hulihan,
D.W.Dickson,
Z.K.Wszolek,
R.J.Uitti,
N.R.Graff-Radford,
B.F.Boeve,
K.A.Josephs,
B.Miller,
K.B.Boylan,
K.Gwinn,
C.H.Adler,
J.O.Aasly,
F.Hentati,
A.Destée,
A.Krygowska-Wajs,
M.C.Chartier-Harlin,
O.A.Ross,
R.Rademakers,
and
M.J.Farrer
(2009).
Characterization of DCTN1 genetic variability in neurodegeneration.
|
| |
Neurology,
72,
2024-2028.
|
|
|
|
|
|
|
E.J.Tisdale,
F.Azizi,
and
C.R.Artalejo
(2009).
Rab2 Utilizes Glyceraldehyde-3-phosphate Dehydrogenase and Protein Kinase C{iota} to Associate with Microtubules and to Recruit Dynein.
|
| |
J Biol Chem,
284,
5876-5884.
|
|
|
|
|
|
|
F.Achilli,
V.Bros-Facer,
H.P.Williams,
G.T.Banks,
M.AlQatari,
R.Chia,
V.Tucci,
M.Groves,
C.D.Nickols,
K.L.Seburn,
R.Kendall,
M.Z.Cader,
K.Talbot,
J.van Minnen,
R.W.Burgess,
S.Brandner,
J.E.Martin,
M.Koltzenburg,
L.Greensmith,
P.M.Nolan,
and
E.M.Fisher
(2009).
An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy.
|
| |
Dis Model Mech,
2,
359-373.
|
|
|
|
|
|
|
J.K.Moore,
D.Sept,
and
J.A.Cooper
(2009).
Neurodegeneration mutations in dynactin impair dynein-dependent nuclear migration.
|
| |
Proc Natl Acad Sci U S A,
106,
5147-5152.
|
|
|
|
|
|
|
J.K.Moore,
M.D.Stuchell-Brereton,
and
J.A.Cooper
(2009).
Function of dynein in budding yeast: mitotic spindle positioning in a polarized cell.
|
| |
Cell Motil Cytoskeleton,
66,
546-555.
|
|
|
|
|
|
|
J.Kapitán,
D.Gallo,
N.Goasdoué,
M.Nicaise,
M.Desmadril,
L.Hecht,
G.Leclercq,
L.D.Barron,
and
Y.Jacquot
(2009).
Identification of a human estrogen receptor alpha-derived antiestrogenic peptide that adopts a polyproline II conformation.
|
| |
J Pept Sci,
15,
455-464.
|
|
|
|
|
|
|
J.R.Kardon,
and
R.D.Vale
(2009).
Regulators of the cytoplasmic dynein motor.
|
| |
Nat Rev Mol Cell Biol,
10,
854-865.
|
|
|
|
|
|
|
J.van Haren,
K.Draegestein,
N.Keijzer,
J.P.Abrahams,
F.Grosveld,
P.J.Peeters,
D.Moechars,
and
N.Galjart
(2009).
Mammalian Navigators are microtubule plus-end tracking proteins that can reorganize the cytoskeleton to induce neurite-like extensions.
|
| |
Cell Motil Cytoskeleton,
66,
824-838.
|
|
|
|
|
|
|
K.K.Gupta,
B.A.Paulson,
E.S.Folker,
B.Charlebois,
A.J.Hunt,
and
H.V.Goodson
(2009).
Minimal Plus-end Tracking Unit of the Cytoplasmic Linker Protein CLIP-170.
|
| |
J Biol Chem,
284,
6735-6742.
|
|
|
|
|
|
|
M.J.Farrer,
M.M.Hulihan,
J.M.Kachergus,
J.C.Dächsel,
A.J.Stoessl,
L.L.Grantier,
S.Calne,
D.B.Calne,
B.Lechevalier,
F.Chapon,
Y.Tsuboi,
T.Yamada,
L.Gutmann,
B.Elibol,
K.P.Bhatia,
C.Wider,
C.Vilariño-Güell,
O.A.Ross,
L.A.Brown,
M.Castanedes-Casey,
D.W.Dickson,
and
Z.K.Wszolek
(2009).
DCTN1 mutations in Perry syndrome.
|
| |
Nat Genet,
41,
163-165.
|
|
|
|
|
|
|
O.N.Zhapparova,
S.A.Bryantseva,
L.V.Dergunova,
N.M.Raevskaya,
A.V.Burakov,
O.B.Bantysh,
N.A.Shanina,
and
E.S.Nadezhdina
(2009).
Dynactin subunit p150Glued isoforms notable for differential interaction with microtubules.
|
| |
Traffic,
10,
1635-1646.
|
|
|
|
|
|
|
R.H.Wade
(2009).
On and around microtubules: an overview.
|
| |
Mol Biotechnol,
43,
177-191.
|
|
|
|
|
|
|
S.Honnappa,
S.M.Gouveia,
A.Weisbrich,
F.F.Damberger,
N.S.Bhavesh,
H.Jawhari,
I.Grigoriev,
F.J.van Rijssel,
R.M.Buey,
A.Lawera,
I.Jelesarov,
F.K.Winkler,
K.Wüthrich,
A.Akhmanova,
and
M.O.Steinmetz
(2009).
An EB1-binding motif acts as a microtubule tip localization signal.
|
| |
Cell,
138,
366-376.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Y.Komarova,
C.O.De Groot,
I.Grigoriev,
S.M.Gouveia,
E.L.Munteanu,
J.M.Schober,
S.Honnappa,
R.M.Buey,
C.C.Hoogenraad,
M.Dogterom,
G.G.Borisy,
M.O.Steinmetz,
and
A.Akhmanova
(2009).
Mammalian end binding proteins control persistent microtubule growth.
|
| |
J Cell Biol,
184,
691-706.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
A.Akhmanova,
and
M.O.Steinmetz
(2008).
Tracking the ends: a dynamic protein network controls the fate of microtubule tips.
|
| |
Nat Rev Mol Cell Biol,
9,
309-322.
|
|
|
|
|
|
|
G.Tian,
X.P.Kong,
X.H.Jaglin,
J.Chelly,
D.Keays,
and
N.J.Cowan
(2008).
A Pachygyria-causing {alpha}-Tubulin Mutation Results in Inefficient Cycling with CCT and a Deficient Interaction with TBCB.
|
| |
Mol Biol Cell,
19,
1152-1161.
|
|
|
|
|
|
|
J.W.Hammond,
D.Cai,
and
K.J.Verhey
(2008).
Tubulin modifications and their cellular functions.
|
| |
Curr Opin Cell Biol,
20,
71-76.
|
|
|
|
|
|
|
M.O.Steinmetz,
and
A.Akhmanova
(2008).
Capturing protein tails by CAP-Gly domains.
|
| |
Trends Biochem Sci,
33,
535-545.
|
|
|
|
|
|
|
P.Bieling,
S.Kandels-Lewis,
I.A.Telley,
J.van Dijk,
C.Janke,
and
T.Surrey
(2008).
CLIP-170 tracks growing microtubule ends by dynamically recognizing composite EB1/tubulin-binding sites.
|
| |
J Cell Biol,
183,
1223-1233.
|
|
|
|
|
|
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.
|
 |
|
Links
