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PDBsum entry 3fso
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Cell adhesion
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PDB id
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3fso
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References listed in PDB file
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Key reference
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Title
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Structure of the calx-Beta domain of the integrin beta4 subunit: insights into function and cation-Independent stability.
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Authors
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N.Alonso-García,
A.Inglés-Prieto,
A.Sonnenberg,
J.M.De pereda.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2009,
65,
858-871.
[DOI no: ]
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PubMed id
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Abstract
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The integrin alpha6beta4 is a receptor for laminins and provides stable adhesion
of epithelial cells to the basement membranes. In addition, alpha6beta4 is
important for keratinocyte migration during wound healing and favours the
invasion of carcinomas into surrounding tissue. The cytoplasmic domain of the
beta4 subunit is responsible for most of the intracellular interactions of the
integrin; it contains four fibronectin type III domains and a Calx-beta motif.
The crystal structure of the Calx-beta domain of beta4 was determined to 1.48 A
resolution. The structure does not contain cations and biophysical data support
the supposition that the Calx-beta domain of beta4 does not bind calcium.
Comparison of the Calx-beta domain of beta4 with the calcium-binding domains of
Na(+)/Ca(2+)-exchanger 1 reveals that in beta4 Arg1003 occupies a position
equivalent to that of the calcium ions in the Na(+)/Ca(2+)-exchanger. By
combining mutagenesis and thermally induced unfolding, it is shown that Arg1003
contributes to the stability of the Calx-beta domain. The structure of the
Calx-beta domain is discussed in the context of the function and intracellular
interactions of the integrin beta4 subunit and a putative functional site is
proposed.
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Figure 3.
Figure 3 Structure of the BC, DE and FG loops of  4.
(a) Close-up view of the BC (yellow) and DE (pink) loops; the
side chain of R1014 plays a central role in the stabilization of
this region by establishing hydrogen bonds within the BC loop
and with the backbone of the DE loop. D990 in the N-terminus
(grey) makes a hydrogen bond to the backbone of the BC loop. (b)
Detailed view of the -hairpin
at the FG loop. The relative position of the residues that form
the type I' -turn
(1087-1090) is shown in parentheses. Hydrogen bonds are shown as
dashed lines.
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Figure 5.
Figure 5 Stereo representations of simulated-annealing OMIT
maps of the pseudo-Ca^2+-binding sites of the 4
structures. (a) Structure of molecule A of the asymmetric unit
of the native crystal. (b) Structure of molecule B of the
asymmetric unit of the native crystal. (c) and (d) show the
structures of molecule A and molecule B crystallized in the
presence of 2 mM Ca^2+, respectively. Each map (2mF[obs] -
DF[calc], contoured at 1  )
was calculated after performing a round of refinement using
simulated annealing (initial temperature 5000 K) of models from
which the regions shown in the figure were removed. No
significant differences were observed in the protein and solvent
network between the equivalent molecules of the native and
Ca^2+-cocrystallized structures.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2009,
65,
858-871)
copyright 2009.
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