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* Residue conservation analysis
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PDB id:
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Actin-binding
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Title:
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Gelsolin g4-g6/actin complex
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Structure:
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Actin. Chain: a. Gelsolin. Chain: g. Fragment: g4-g6, residues 412-742 of cytoplasmic isoform. Synonym: actin-depolymerizing factor, brevin, agel. Engineered: yes
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Source:
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Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Tissue: muscle. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Biol. unit:
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Dimer (from PDB file)
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Resolution:
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2.99Å
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R-factor:
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0.219
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R-free:
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0.268
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Authors:
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H.Choe,L.D.Burtnick,M.Mejillano,H.L.Yin,R.C.Robinson,S.Choe
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Key ref:
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H.Choe
et al.
(2002).
The calcium activation of gelsolin: insights from the 3A structure of the G4-G6/actin complex.
J Mol Biol,
324,
691-702.
PubMed id:
DOI:
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Date:
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23-Jul-02
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Release date:
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24-Jan-03
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Supersedes:
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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
324:691-702
(2002)
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PubMed id:
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The calcium activation of gelsolin: insights from the 3A structure of the G4-G6/actin complex.
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H.Choe,
L.D.Burtnick,
M.Mejillano,
H.L.Yin,
R.C.Robinson,
S.Choe.
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ABSTRACT
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Gelsolin participates in the reorganization of the actin cytoskeleton that is
required during such phenomena as cell movement, cytokinesis, and apoptosis. It
consists of six structurally similar domains, G1-G6, which are arranged at
resting intracellular levels of calcium ion so as to obscure the three
actin-binding surfaces. Elevation of Ca(2+) concentrations releases latches
within the constrained structure and produces large shifts in the relative
positioning of the domains, permitting gelsolin to bind to and sever actin
filaments. How Ca(2+) is able to activate gelsolin has been a major question
concerning the function of this protein. We present the improved structure of
the C-terminal half of gelsolin bound to monomeric actin at 3.0 A resolution.
Two classes of Ca(2+)-binding site are evident on gelsolin: type 1 sites share
coordination of Ca(2+) with actin, while type 2 sites are wholly contained
within gelsolin. This structure of the complex reveals the locations of two
novel metal ion-binding sites in domains G5 and G6, respectively. We identify
both as type 2 sites. The absolute conservation of the type 2 calcium-ligating
residues across the six domains of gelsolin suggests that this site exists in
each of the domains. In total, gelsolin has the potential to bind eight calcium
ions, two type 1 and six type 2. The function of the type 2 sites is to
facilitate structural rearrangements within gelsolin as part of the activation
and actin-binding and severing processes. We propose the novel type 2 site in G6
to be the critical site that initiates overall activation of gelsolin by
releasing the tail latch that locks calcium-free gelsolin in a conformation
unable to bind actin.
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Selected figure(s)
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Figure 1.
Figure 1. Ribbon diagram of gelsolin domains G4-G6 showing
the conformational changes on binding calcium and actin. Actin
is shown in cyan, G4 in pink, G5 in green, and G6 is painted
orange. The left-hand panel shows G4-G6 in a calcium-free
conformation.[2.] The right hand panel depicts the actin and
calcium-bound form of G4-G6 as reported here. Ca^2+ in the type
1 site on G4 (gold sphere) is sandwiched between G4 and actin.
Calcium ions occupy each of the type 2 sites (gray spheres) in
all three gelsolin domains.
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Figure 2.
Figure 2. Type 1 calcium ion-binding sites. Ca^2+ in type 1
sites in G1 and in G4 is coordinated by Glu167 of actin (cyan).
In severin domain 2,[16.] the structure of which was elucidated
in the absence of actin, a water molecule (purple) completes the
coordination sphere of Ca^2+. This site is characterized by
coordination by a conserved aspartic acid at the C-terminal end
of the H1 helix and carbonyl oxygen atoms five and seven
residues further along the polypeptide chain. Calcium ions are
shown as gold spheres.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2002,
324,
691-702)
copyright 2002.
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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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E.Karaca,
and
A.M.Bonvin
(2011).
A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes.
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Structure,
19,
555-565.
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Y.Zhang,
Y.Xiao,
F.Du,
L.Cao,
H.Dong,
and
H.Ren
(2011).
Arabidopsis VILLIN4 is involved in root hair growth through regulating actin organization in a Ca2+-dependent manner.
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New Phytol,
190,
667-682.
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A.Van den Abbeele,
S.De Clercq,
A.De Ganck,
V.De Corte,
B.Van Loo,
S.H.Soror,
V.Srinivasan,
J.Steyaert,
J.Vandekerckhove,
and
J.Gettemans
(2010).
A llama-derived gelsolin single-domain antibody blocks gelsolin-G-actin interaction.
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Cell Mol Life Sci,
67,
1519-1535.
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PDB codes:
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H.Wang,
S.Chumnarnsilpa,
A.Loonchanta,
Q.Li,
Y.M.Kuan,
S.Robine,
M.Larsson,
I.Mihalek,
L.D.Burtnick,
and
R.C.Robinson
(2009).
Helix straightening as an activation mechanism in the gelsolin superfamily of actin regulatory proteins.
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J Biol Chem,
284,
21265-21269.
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PDB code:
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S.Chumnarnsilpa,
W.L.Lee,
S.Nag,
B.Kannan,
M.Larsson,
L.D.Burtnick,
and
R.C.Robinson
(2009).
The crystal structure of the C-terminus of adseverin reveals the actin-binding interface.
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Proc Natl Acad Sci U S A,
106,
13719-13724.
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PDB code:
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S.Nag,
Q.Ma,
H.Wang,
S.Chumnarnsilpa,
W.L.Lee,
M.Larsson,
B.Kannan,
M.Hernandez-Valladares,
L.D.Burtnick,
and
R.C.Robinson
(2009).
Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin.
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Proc Natl Acad Sci U S A,
106,
13713-13718.
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PDB codes:
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C.M.Hampton,
J.Liu,
D.W.Taylor,
D.J.DeRosier,
and
K.A.Taylor
(2008).
The 3D structure of villin as an unusual F-Actin crosslinker.
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Structure,
16,
1882-1891.
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I.Aprodu,
A.Redaelli,
and
M.Soncini
(2008).
Actomyosin interaction: mechanical and energetic properties in different nucleotide binding States.
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Int J Mol Sci,
9,
1927-1943.
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S.Bär,
L.Daeffler,
J.Rommelaere,
and
J.P.Nüesch
(2008).
Vesicular egress of non-enveloped lytic parvoviruses depends on gelsolin functioning.
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PLoS Pathog,
4,
e1000126.
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Ashish,
M.S.Paine,
P.B.Perryman,
L.Yang,
H.L.Yin,
and
J.K.Krueger
(2007).
Global structure changes associated with Ca2+ activation of full-length human plasma gelsolin.
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J Biol Chem,
282,
25884-25892.
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C.Revenu,
M.Courtois,
A.Michelot,
C.Sykes,
D.Louvard,
and
S.Robine
(2007).
Villin severing activity enhances actin-based motility in vivo.
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Mol Biol Cell,
18,
827-838.
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V.O.Paavilainen,
M.Hellman,
E.Helfer,
M.Bovellan,
A.Annila,
M.F.Carlier,
P.Permi,
and
P.Lappalainen
(2007).
Structural basis and evolutionary origin of actin filament capping by twinfilin.
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Proc Natl Acad Sci U S A,
104,
3113-3118.
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PDB code:
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E.D.Grimm,
R.V.Portugal,
M.de Oliveira Neto,
N.H.Martins,
I.Polikarpov,
A.Zaha,
and
H.B.Ferreira
(2006).
Structural analysis of an Echinococcus granulosus actin-fragmenting protein by small-angle x-ray scattering studies and molecular modeling.
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Biophys J,
90,
3216-3223.
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E.Helfer,
E.M.Nevalainen,
P.Naumanen,
S.Romero,
D.Didry,
D.Pantaloni,
P.Lappalainen,
and
M.F.Carlier
(2006).
Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility.
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EMBO J,
25,
1184-1195.
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A.H.Aguda,
L.D.Burtnick,
and
R.C.Robinson
(2005).
The state of the filament.
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EMBO Rep,
6,
220-226.
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H.Gong,
V.Hatch,
L.Ali,
W.Lehman,
R.Craig,
and
L.S.Tobacman
(2005).
Mini-thin filaments regulated by troponin-tropomyosin.
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Proc Natl Acad Sci U S A,
102,
656-661.
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B.J.Pope,
K.M.Zierler-Gould,
R.Kühne,
A.G.Weeds,
and
L.J.Ball
(2004).
Solution structure of human cofilin: actin binding, pH sensitivity, and relationship to actin-depolymerizing factor.
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J Biol Chem,
279,
4840-4848.
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PDB codes:
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L.D.Burtnick,
D.Urosev,
E.Irobi,
K.Narayan,
and
R.C.Robinson
(2004).
Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF.
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EMBO J,
23,
2713-2722.
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PDB code:
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N.Kumar,
A.Tomar,
A.L.Parrill,
and
S.Khurana
(2004).
Functional dissection and molecular characterization of calcium-sensitive actin-capping and actin-depolymerizing sites in villin.
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J Biol Chem,
279,
45036-45046.
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N.Kumar,
and
S.Khurana
(2004).
Identification of a functional switch for actin severing by cytoskeletal proteins.
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J Biol Chem,
279,
24915-24918.
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S.Huang,
L.Blanchoin,
F.Chaudhry,
V.E.Franklin-Tong,
and
C.J.Staiger
(2004).
A gelsolin-like protein from Papaver rhoeas pollen (PrABP80) stimulates calcium-regulated severing and depolymerization of actin filaments.
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J Biol Chem,
279,
23364-23375.
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Z.Zhang,
and
S.L.Stanley
(2004).
Stereotypic and specific elements of the human colonic response to Entamoeba histolytica and Shigella flexneri.
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Cell Microbiol,
6,
535-554.
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E.Lagarrigue,
D.Ternent,
S.K.Maciver,
A.Fattoum,
Y.Benyamin,
and
C.Roustan
(2003).
The activation of gelsolin by low pH: the calcium latch is sensitive to calcium but not pH.
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Eur J Biochem,
270,
4105-4112.
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E.Lagarrigue,
S.K.Maciver,
A.Fattoum,
Y.Benyamin,
and
C.Roustan
(2003).
Co-operation of domain-binding and calcium-binding sites in the activation of gelsolin.
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Eur J Biochem,
270,
2236-2243.
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J.G.Kiselar,
P.A.Janmey,
S.C.Almo,
and
M.R.Chance
(2003).
Visualizing the Ca2+-dependent activation of gelsolin by using synchrotron footprinting.
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Proc Natl Acad Sci U S A,
100,
3942-3947.
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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
