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PDBsum entry 4dx9
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Protein binding
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PDB id
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4dx9
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Contents |
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106 a.a.
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110 a.a.
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105 a.a.
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127 a.a.
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(+ 9 more)
11 a.a.
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118 a.a.
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127 a.a.
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91 a.a.
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113 a.a.
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104 a.a.
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(+ 1 more)
127 a.a.
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63 a.a.
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47 a.a.
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129 a.a.
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116 a.a.
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102 a.a.
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99 a.a.
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102 a.a.
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106 a.a.
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120 a.a.
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101 a.a.
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101 a.a.
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128 a.a.
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49 a.a.
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12 a.a.
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93 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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Mechanism for krit1 release of icap1-Mediated suppression of integrin activation.
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Authors
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W.Liu,
K.M.Draheim,
R.Zhang,
D.A.Calderwood,
T.J.Boggon.
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Ref.
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Mol Cell, 2013,
49,
719-729.
[DOI no: ]
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PubMed id
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Abstract
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KRIT1 (Krev/Rap1 Interaction Trapped-1) mutations are observed in ∼40% of
autosomal-dominant cerebral cavernous malformations (CCMs), a disease occurring
in up to 0.5% of the population. We show that KRIT1 functions as a switch for
β1 integrin activation by antagonizing ICAP1 (Integrin Cytoplasmic Associated
Protein-1)-mediated modulation of "inside-out" activation. We present
cocrystal structures of KRIT1 with ICAP1 and ICAP1 with integrin β1 cytoplasmic
tail to 2.54 and 3.0 Å resolution (the resolutions at which I/σI = 2 are
2.75 and 3.0 Å, respectively). We find that KRIT1 binds ICAP1 by a bidentate
surface, that KRIT1 directly competes with integrin β1 to bind ICAP1, and that
KRIT1 antagonizes ICAP1-modulated integrin activation using this site. We also
find that KRIT1 contains an N-terminal Nudix domain, in a region previously
designated as unstructured. We therefore provide insights to integrin regulation
and CCM-associated KRIT1 function.
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