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PDBsum entry 1h1v
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Actin-binding
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PDB id
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1h1v
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The calcium activation of gelsolin: insights from the 3a structure of the g4-G6/actin complex.
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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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Ref.
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J Mol Biol, 2002,
324,
691-702.
[DOI no: ]
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PubMed id
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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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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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Secondary reference #1
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Title
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Domain movement in gelsolin: a calcium-Activated switch.
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Authors
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R.C.Robinson,
M.Mejillano,
V.P.Le,
L.D.Burtnick,
H.L.Yin,
S.Choe.
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Ref.
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Science, 1999,
286,
1939-1942.
[DOI no: ]
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PubMed id
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Figure 2.
Fig. 2. Comparison of the G1 and G4 actin-binding sites. (A)
Surface representations of G1 and G4 detailing residues at the
actin-gelsolin interface. Charged residues, hydrophobic
residues, and nonconserved residues are colored red, yellow, and
green, respectively. (B) Actin-bound forms of G1 (5) (red) and
G4 (pink) in about the same orientation as in (A) are shown as
schematic representations. Bound calcium ions are shown as black
spheres. Type 1 calcium ions are labeled 1Ca2+ and type 2 are
labeled 2Ca2+.
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Figure 4.
Fig. 4. Proposed model of the gelsolin-two-actin complex.
Schematic representations of two copies of the G4-G6-actin
complex are oriented so that the actin protomers are related
according to the Holmes model of the actin filament (9).
Gelsolin domains G4, G5, and G6 bound to actin protomer 1 are
labeled G1, G2, and G3, respectively. The actin filament is
oriented to run vertically in the plane of the paper, indicated
by the arrow (cyan) as in Fig. 1A. The COOH-terminus of G3
(labeled C) and the NH[2]-terminus of G4 (labeled N) are 66
Å apart in this model.
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The above figures are
reproduced from the cited reference
with permission from the AAAs
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