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PDBsum entry 2kbb
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Structural protein
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PDB id
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2kbb
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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 structure of an interdomain complex which regulates talin activity.
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Authors
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B.T.Goult,
N.Bate,
N.J.Anthis,
K.L.Wegener,
A.R.Gingras,
B.Patel,
I.L.Barsukov,
I.D.Campbell,
G.C.Roberts,
D.R.Critchley.
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Ref.
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J Biol Chem, 2009,
284,
15097-15106.
[DOI no: ]
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PubMed id
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Abstract
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Talin is a large flexible rod-shaped protein that activates the integrin family
of cell adhesion molecules and couples them to cytoskeletal actin. It exists in
both globular and extended conformations, and an intra-molecular interaction
between the N-terminal F3 FERM sub-domain and the C-terminal part of the talin
rod contributes to an autoinhibited form of the molecule. Here, we report the
solution structure of the primary F3 binding domain within the C-terminal region
of the talin rod and use intermolecular NOEs to determine the structure of the
complex. The rod domain (residues 1655-1822) is an amphipathic 5-helix bundle -
Y377 of F3 docks into a hydrophobic pocket at one end of the bundle whilst a
basic loop in F3 (residues 316 to 326) interacts with a cluster of acidic
residues in the middle of helix 4. Mutation of E1770 abolishes binding. The rod
domain competes with beta3-integrin tails for binding to F3 and the structure of
the complex suggests that the rod is also likely to sterically inhibit binding
of the FERM domain to the membrane.
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Figure 1.
Structure of the talin 1655–1822 rod domain. A, schematic
representation of the domain structure of talin indicating the
relative position of the ligand binding sites and the boundaries
of the various head and rod domains. B, sequence alignment of
human talin1 residues 1655–1822 with the corresponding regions
of other talins. C, superimposition of the 20 lowest energy
structures consistent with the NMR data. Only the structured
region of 1655–1822 is shown, not the disordered N terminus.
D, ribbon drawing of a representative low energy structure
showing the overall topology of the five-helix bundle. E, map of
the surface charge of the domain.
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Figure 3.
Structure of the complex between talin F3 and talin
1655–1822. A, ribbon representation of the model of talin F3
(red) in complex with talin 1655–1822 (pale blue) obtained
using the HADDOCK approach. B, close-up of the interface showing
Tyr-377 of F3 and its close proximity to Leu-1680, Val-1683,
Met-1759, and Leu-1762 of talin 1655–1822. C, close-up of the
interaction of the positively charged activation loop of F3 with
the negatively charged residues on talin 1655–1822.
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The above figures are
reprinted
from an Open Access publication published by the ASBMB:
J Biol Chem
(2009,
284,
15097-15106)
copyright 2009.
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