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1dpk

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[[Image:1dpk.jpg|left|200px]]<br /><applet load="1dpk" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1dpk.jpg|left|200px]]
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caption="1dpk" />
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'''SOLUTION STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE INTEGRIN ALPHA-IIB SUBUNIT'''<br />
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{{Structure
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|PDB= 1dpk |SIZE=350|CAPTION= <scene name='initialview01'>1dpk</scene>
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|SITE=
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|LIGAND=
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|ACTIVITY=
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|GENE=
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}}
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'''SOLUTION STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE INTEGRIN ALPHA-IIB SUBUNIT'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1DPK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DPK OCA].
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1DPK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DPK OCA].
==Reference==
==Reference==
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A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit., Vinogradova O, Haas T, Plow EF, Qin J, Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1450-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10677482 10677482]
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A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit., Vinogradova O, Haas T, Plow EF, Qin J, Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1450-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10677482 10677482]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Haas, T.]]
[[Category: Haas, T.]]
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[[Category: helix-turn]]
[[Category: helix-turn]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:19:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:42:13 2008''

Revision as of 08:42, 20 March 2008


PDB ID 1dpk

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SOLUTION STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE INTEGRIN ALPHA-IIB SUBUNIT


Contents

Overview

A key step in the activation of heterodimeric integrin adhesion receptors is the transmission of an agonist-induced cellular signal from the short alpha- and/or beta-cytoplasmic tails to the extracellular domains of the receptor. The structural details of how the cytoplasmic tails mediate such an inside-out signaling process remain unclear. We report herein the NMR structures of a membrane-anchored cytoplasmic tail of the alpha(IIb)-subunit and of a mutant alpha(IIb)-cytoplasmic tail that renders platelet integrin alpha(IIb)beta(3) constitutively active. The structure of the wild-type alpha(IIb)-cytoplasmic tail reveals a "closed" conformation where the highly conserved N-terminal membrane-proximal region forms an alpha-helix followed by a turn, and the acidic C-terminal loop interacts with the N-terminal helix. The structure of the active mutant is significantly different, having an "open" conformation where the interactions between the N-terminal helix and C-terminal region are abolished. Consistent with these structural differences, the two peptides differ in function: the wild-type peptide suppressed alpha(IIb)beta(3) activation, whereas the mutant peptide did not. These results provide an atomic explanation for extensive biochemical/mutational data and support a conformation-based "on/off switch" model for integrin activation.

Disease

Known diseases associated with this structure: Glanzmann thrombasthenia, type A OMIM:[607759], Thrombocytopenia, neonatal alloimmune OMIM:[607759]

About this Structure

1DPK is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit., Vinogradova O, Haas T, Plow EF, Qin J, Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1450-5. PMID:10677482

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