2lko

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[[Image:2lko.png|left|200px]]
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==Structural Basis of Phosphoinositide Binding to Kindlin-2 Pleckstrin Homology Domain in Regulating Integrin Activation==
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<StructureSection load='2lko' size='340' side='right' caption='[[2lko]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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== Structural highlights ==
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[[2lko]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKO OCA]. <br>
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<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
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== Publication Abstract from PubMed ==
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Kindlins are a subclass of FERM-containing proteins that have recently emerged as key regulators of integrin receptor activation and signaling. As compared with the conventional FERM domain, the kindlin FERM domain contains an inserted pleckstrin homology (PH) domain that recognizes membrane phosphoinositides, including phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). Using NMR spectroscopy, we show that PIP3 site-specifically binds to kindlin-2 PH with substantial chemical shift changes that are much larger than PIP2. This suggests an enhanced association of kindlin-2 with membrane as mediated by PIP3 upon its conversion from PIP2 by phosphoinositide-3 kinase, a known regulator of integrin activation. We determined the NMR structure of the kindlin-2 PH domain bound to the head group of PIP3, inositol 1,3,4,5-tetraphosphate (IP4). The structure reveals a canonical PH domain fold, yet with a distinct IP4 binding pocket that appears highly conserved for the kindlin family members. Functional experiments demonstrate that although wild type kindlin-2 is capable of cooperating with integrin activator talin to induce synergistic integrin alpha(IIb)beta(3) activation, this ability is significantly impaired for a phosphoinositide binding-defective kindlin-2 mutant. These results define a specific PIP3 recognition mode for the kindlin PH domain. Moreover, they shed light upon a mechanism as to how the PH domain mediates membrane engagement of kindlin-2 to promote its binding to integrin and cooperation with talin for regulation of integrin activation.
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Structural basis of phosphoinositide binding to kindlin-2 protein pleckstrin homology domain in regulating integrin activation.,Liu J, Fukuda K, Xu Z, Ma YQ, Hirbawi J, Mao X, Wu C, Plow EF, Qin J J Biol Chem. 2011 Dec 16;286(50):43334-42. Epub 2011 Oct 26. PMID:22030399<ref>PMID:22030399</ref>
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The line below this paragraph, containing "STRUCTURE_2lko", creates the "Structure Box" on the page.
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{{STRUCTURE_2lko| PDB=2lko | SCENE= }}
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===Structural Basis of Phosphoinositide Binding to Kindlin-2 Pleckstrin Homology Domain in Regulating Integrin Activation===
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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== References ==
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<references/>
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(as it appears on PubMed at http://www.pubmed.gov), where 22030399 is the PubMed ID number.
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{{ABSTRACT_PUBMED_22030399}}
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==About this Structure==
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[[2lko]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKO OCA].
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==Reference==
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<ref group="xtra">PMID:022030399</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Fukuda, K.]]
[[Category: Fukuda, K.]]

Revision as of 08:29, 30 April 2014

Structural Basis of Phosphoinositide Binding to Kindlin-2 Pleckstrin Homology Domain in Regulating Integrin Activation

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