Cell Junctions, Structure, Function, and Regulation
337
(b) Hypothesized
intermediate in activation
by RGD or Mn
2
+
(c) Hypothesized
intermediate in activation
by inside-out signaling
(d) Extended
conformer
with closed
headpiece
(intermediate
affinity)
(e) Extended
conformer
with open
headpiece
(high
affinity)
(a) Bent conformer
(low affinity)
Fig. 4
Conformational changes in integrin structure associated with integrin activation.
Results from X-Ray crystallography, electron microscopy and mutational studies suggest
that integrins with different ligand-binding afFnities have different conformations.
Integrins with a bent structure are in the low afFnity conformation (a), whereas Sho
integrins with an extended structure with an open headpiece (consisting of the globular
ligand-binding domains) are in the high afFnity conformation (e). Integrins in
intermediate afFnity conformations have extended structures, but with closed headpieces
(d). Other intermediate afFnity conformations have been hypothesized (b and c).
(Reprinted with permission from Takagi, J., Petre, B.M., Walz, T., Springer, T.A. (2002)
Global conformational rearrangements in integrin extracellular domains in outside-in and
inside-out signaling,
Cell
110
, 599–611).
tails is sufFcient to activate tyrosine kinase
and Rac signaling.
The eight integrin
β
-tails have varying
degrees of amino acid homology (±ig. 5)
with the
β
1
2
,and
β
3
tails showing the
most similarity. Not surprisingly, several
proteins have been shown to bind to more
than one of these
β
-tails, whereas other
protein interactions are
β
-tail speciFc. The
β
8
tail has no homology with other integrin
β
-tails and to date no proteins have been
identiFed that bind to the
β
8
tail. The
β
4
tail shows no similarity with other
β
tails
except that it contains NPXY and NXXY
motifs that are present in other
β
-tails.
Protein interactions with the
β
4
tail will be
discussed in Sect. 1.5.
The
β
1
2
and
β
3
cytoplasmic tails share
considerable amino acid sequence homol-
ogy and the cytoskeletal linker protein talin
hasbeenshowntob
indtoa
l
lthreeta
i
ls
.
Since talin binds to actin and the actin
binding protein vinculin, integrin-talin in-
teractions are likely to regulate many
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