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PDBsum entry 2v7q
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Contents |
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487 a.a.
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469 a.a.
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263 a.a.
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131 a.a.
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47 a.a.
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43 a.a.
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References listed in PDB file
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Key reference
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Title
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How the regulatory protein, If(1), Inhibits f(1)-Atpase from bovine mitochondria.
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Authors
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J.R.Gledhill,
M.G.Montgomery,
A.G.Leslie,
J.E.Walker.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
15671-15676.
[DOI no: ]
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PubMed id
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Abstract
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The structure of bovine F(1)-ATPase inhibited by a monomeric form of the
inhibitor protein, IF(1), known as I1-60His, lacking most of the dimerization
region, has been determined at 2.1-A resolution. The resolved region of the
inhibitor from residues 8-50 consists of an extended structure from residues
8-13, followed by two alpha-helices from residues 14-18 and residues 21-50
linked by a turn. The binding site in the beta(DP)-alpha(DP) catalytic interface
is complex with contributions from five different subunits of F(1)-ATPase. The
longer helix extends from the external surface of F(1) via a deep groove made
from helices and loops in the C-terminal domains of subunits beta(DP),
alpha(DP), beta(TP), and alpha(TP) to the internal cavity surrounding the
central stalk. The linker and shorter helix interact with the gamma-subunit in
the central stalk, and the N-terminal region extends across the central cavity
to interact with the nucleotide binding domain of the alpha(E) subunit. To form
these complex interactions and penetrate into the core of the enzyme, it is
likely that the initial interaction of the inhibitor with F(1) forms via the
open conformation of the beta(E) subunit. Then, as two ATP molecules are
hydrolyzed, the beta(E)-alpha(E) interface converts to the beta(DP)-alpha(DP)
interface via the beta(TP)-alpha(TP) interface, trapping the inhibitor
progressively in its binding site and a nucleotide in the catalytic site of
subunit beta(DP). The inhibition probably arises by IF(1) imposing the structure
and properties of the beta(TP)-alpha(TP) interface on the beta(DP)-alpha(DP)
interface, thereby preventing it from hydrolyzing the bound ATP.
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Figure 1.
Fig. 1. The structure of the bovine F[1]-I1–60His
complex. (A) Overall view of the complex. The  -,  -,  -,  -, and
 -subunits are shown in
ribbon form in red, yellow, dark blue, magenta, and green,
respectively. Residues 8–50 of I1–60His are shown in light
blue solid representation. (B) View upward (away from the foot
of the central stalk), along the axis of the -subunit showing the
orientation of the long -helix of I1–60His
relative to the C-terminal domains of the - and -subunits. The N- and
C-terminal ends of the I1–60His are labeled N and C,
respectively.
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Figure 2.
Fig. 2. The binding site for I1–60His in bovine
F[1]-ATPase. (A and B) Ribbon and solid representations,
respectively, of the binding site groove formed from -helices
and loops between them in the C-terminal domains of the [DP]-,
[DP]-, and [TP]-
subunits, occupied by the long helix (residues 21–50) of
I1–60His (light blue). The N- and C-terminal ends of the
I1–60HIS are labeled N and C, respectively, in A. (B) The
orange side chains are those of the strictly conserved residues
Lys-24, Arg-25, and Glu-26 of I1–60His that do not interact
with F[1]-ATPase. (C and D) Interactions between residues 8–46
and F[1]-ATPase. (C) View from the side of the central stalk
showing the orientation of I1–60His relative to the -subunit. The N- and
C-terminal ends of the I1–60HIS are labeled N and C,
respectively. (D) View down along the axis of the -subunit
showing the interaction of the short helix with the -subunit
and the interaction between the extended region formed by
residues 10–12 of I1–60His and side chains in the nucleotide
binding domain of the [E]-subunit.
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