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New page: left|200px<br /> <applet load="1fb8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fb8, resolution 2.40Å" /> '''STRUCTURE OF THE PL...
 
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[[Image:1fb8.gif|left|200px]]<br />
<applet load="1fb8" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1fb8, resolution 2.40&Aring;" />
'''STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN FROM DAPP1/PHISH'''<br />


==Overview==
==STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN FROM DAPP1/PHISH==
Pleckstrin homology (PH) domains are protein modules of around 120 amino, acids found in many proteins involved in cellular signaling. Certain PH, domains drive signal-dependent membrane recruitment of their host proteins, by binding strongly and specifically to lipid second messengers produced, by agonist-stimulated phosphoinositide 3-kinases (PI 3-Ks). We describe, X-ray crystal structures of two different PH domains bound to, Ins(1,3,4,5)P4, the head group of the major PI 3-K product, PtdIns(3,4,5)P3. One of these PH domains (from Grp1) is PtdIns(3,4,5)P3, specific, while the other (from DAPP1/PHISH) binds strongly to both, PtdIns(3,4,5)P3 and its 5'-dephosphorylation product, PtdIns(3,4)P2., Comparison of the two structures provides an explanation for the distinct, phosphoinositide specificities of the two PH domains and allows us to, predict the 3-phosphoinositide selectivity of uncharacterized PH domains.
<StructureSection load='1fb8' size='340' side='right'caption='[[1fb8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fb8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FB8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1fb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fb8 OCA], [https://pdbe.org/1fb8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fb8 RCSB], [https://www.ebi.ac.uk/pdbsum/1fb8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fb8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAPP1_HUMAN DAPP1_HUMAN] May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K.<ref>PMID:10770799</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fb/1fb8_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1fb8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pleckstrin homology (PH) domains are protein modules of around 120 amino acids found in many proteins involved in cellular signaling. Certain PH domains drive signal-dependent membrane recruitment of their host proteins by binding strongly and specifically to lipid second messengers produced by agonist-stimulated phosphoinositide 3-kinases (PI 3-Ks). We describe X-ray crystal structures of two different PH domains bound to Ins(1,3,4,5)P4, the head group of the major PI 3-K product PtdIns(3,4,5)P3. One of these PH domains (from Grp1) is PtdIns(3,4,5)P3 specific, while the other (from DAPP1/PHISH) binds strongly to both PtdIns(3,4,5)P3 and its 5'-dephosphorylation product, PtdIns(3,4)P2. Comparison of the two structures provides an explanation for the distinct phosphoinositide specificities of the two PH domains and allows us to predict the 3-phosphoinositide selectivity of uncharacterized PH domains.


==About this Structure==
Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains.,Ferguson KM, Kavran JM, Sankaran VG, Fournier E, Isakoff SJ, Skolnik EY, Lemmon MA Mol Cell. 2000 Aug;6(2):373-84. PMID:10983984<ref>PMID:10983984</ref>
1FB8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FB8 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains., Ferguson KM, Kavran JM, Sankaran VG, Fournier E, Isakoff SJ, Skolnik EY, Lemmon MA, Mol Cell. 2000 Aug;6(2):373-84. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10983984 10983984]
</div>
<div class="pdbe-citations 1fb8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Ferguson, K.M.]]
[[Category: Ferguson KM]]
[[Category: Fournier, E.]]
[[Category: Fournier E]]
[[Category: Isakoff, S.J.]]
[[Category: Isakoff SJ]]
[[Category: Kavran, J.M.]]
[[Category: Kavran JM]]
[[Category: Lemmon, M.A.]]
[[Category: Lemmon MA]]
[[Category: Sankaran, V.G.]]
[[Category: Sankaran VG]]
[[Category: Skolnik, E.Y.]]
[[Category: Skolnik EY]]
[[Category: PO4]]
[[Category: 3-phosphoinositides]]
[[Category: adaptor protein]]
[[Category: inositol tetrakisphosphate signal transduction protein]]
[[Category: pleckstrin]]
 
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Retrieved from "https://proteopedia.org/1fb8"