View source for 1q2h


==Phenylalanine Zipper Mediates APS Dimerization==
<StructureSection load='1q2h' size='340' side='right'caption='[[1q2h]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1q2h]] is a 3 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=1Q2H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q2H 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]] 1.7&#8491;</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=1q2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q2h OCA], [https://pdbe.org/1q2h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q2h RCSB], [https://www.ebi.ac.uk/pdbsum/1q2h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q2h ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SH2B2_HUMAN SH2B2_HUMAN] Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3.<ref>PMID:10374881</ref> <ref>PMID:9989826</ref> <ref>PMID:12400014</ref> <ref>PMID:15378031</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/q2/1q2h_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=1q2h ConSurf].
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== Publication Abstract from PubMed ==
The APS, SH2-B and LNK proteins are adapters that activate and modulate receptor tyrosine kinase and JAK/STAT signaling. We now show that a conserved N-terminal domain mediates APS homodimerization. We determined the crystal structure of the dimerization domain at a resolution of 1.7 A using bromide ion MAD phasing. Each molecule contributes two helices to a compact four-helix bundle having a bisecting-U topology. Its most conspicuous feature is a stack of interdigitated phenylalanine side chains at the domain core. These residues create a new motif we refer to as a 'phenylalanine zipper,' which is critical to dimerization. A newly developed bridging yeast tri-hybrid assay showed that APS dimerizes JAK2, insulin receptor and IGF1 receptor kinases using its SH2 and dimerization domains. Dimerization via the phenylalanine zipper domain provides a mechanism for activating and modulating tyrosine kinase activity even in the absence of extracellular ligands.

A phenylalanine zipper mediates APS dimerization.,Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI, Shoelson SE Nat Struct Mol Biol. 2004 Oct;11(10):968-74. Epub 2004 Sep 19. PMID:15378031<ref>PMID:15378031</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1q2h" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chi Y-I]]
[[Category: Dhe-Paganon S]]
[[Category: Nishi M]]
[[Category: Shoelson SE]]
[[Category: Werner ED]]