1fu5: Difference between revisions

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[[Image:1fu5.gif|left|200px]]<br /><applet load="1fu5" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1fu5" />
'''NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE COMPLEXED TO A DOUBLY PHOSPHORYLATED PEPTIDE DERIVED FROM POLYOMAVIRUS MIDDLE T ANTIGEN'''<br />


==Overview==
==NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE COMPLEXED TO A DOUBLY PHOSPHORYLATED PEPTIDE DERIVED FROM POLYOMAVIRUS MIDDLE T ANTIGEN==
The N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K) has a higher affinity for a peptide with two phosphotyrosines than for the same peptide with only one. This unexpected result was not observed for the C-terminal SH2 from the same protein. NMR structural analysis has been used to understand the behavior of the N-SH2. The structure of the free SH2 domain has been compared to that of the SH2 complexed with a doubly phosphorylated peptide derived from polyomavirus middle T antigen (MT). The structure of the free SH2 domain shows some differences from previous NMR and X-ray structures. In the N-SH2 complexed with a doubly phosphorylated peptide, a second site for phosphotyrosine interaction has been identified. Further, line shapes of NMR signals showed that the SH2 protein-ligand complex is subject to temperature-dependent conformational mobility. Conformational mobility is also supported by the spectra of the ligand peptide. A binding model which accounts for these results is developed.
<StructureSection load='1fu5' size='340' side='right'caption='[[1fu5]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fu5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_polyomavirus_strain_A3 Murine polyomavirus strain A3] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FU5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=1fu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fu5 OCA], [https://pdbe.org/1fu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fu5 RCSB], [https://www.ebi.ac.uk/pdbsum/1fu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fu5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/P85A_RAT P85A_RAT] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).
== 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/fu/1fu5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1fu5 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1FU5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FU5 OCA].
*[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site., Weber T, Schaffhausen B, Liu Y, Gunther UL, Biochemistry. 2000 Dec 26;39(51):15860-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11123912 11123912]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Murine polyomavirus strain A3]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Guenther, U L.]]
[[Category: Guenther UL]]
[[Category: Liu, Y.]]
[[Category: Liu Y]]
[[Category: Schaffhausen, B.]]
[[Category: Schaffhausen B]]
[[Category: Weber, T.]]
[[Category: Weber T]]
[[Category: protein-peptide complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:42:38 2008''

Latest revision as of 14:16, 27 March 2024

NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE COMPLEXED TO A DOUBLY PHOSPHORYLATED PEPTIDE DERIVED FROM POLYOMAVIRUS MIDDLE T ANTIGENNMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE COMPLEXED TO A DOUBLY PHOSPHORYLATED PEPTIDE DERIVED FROM POLYOMAVIRUS MIDDLE T ANTIGEN

Structural highlights

1fu5 is a 2 chain structure with sequence from Murine polyomavirus strain A3 and Rattus norvegicus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

P85A_RAT Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

Drag the structure with the mouse to rotate

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