View source for 2a36


==Solution structure of the N-terminal SH3 domain of DRK==
<StructureSection load='2a36' size='340' side='right'caption='[[2a36]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2a36]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A36 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2a36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a36 OCA], [https://pdbe.org/2a36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a36 RCSB], [https://www.ebi.ac.uk/pdbsum/2a36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a36 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GRAP_DROME GRAP_DROME] Adapter protein which modulates signaling mediated by several receptor tyrosine kinases such as sev and Ack (PubMed:8462097, PubMed:22615583, PubMed:8462098). Required for proper signaling by sevenless (PubMed:8462097, PubMed:8462098). May act to stimulate the ability of Sos to catalyze Ras1 activation by linking sevenless and Sos in a signaling complex (PubMed:8462097, PubMed:8462098). Required for functional and morphological integrities of the scolopidia, sensory neurons and the antennal mechanosensory and motor center (AMMC) brain neuropil (PubMed:30610177). Required for Ack-dependent suppression of apoptosis in the eye (PubMed:22615583).<ref>PMID:22615583</ref> <ref>PMID:30610177</ref> <ref>PMID:8462097</ref> <ref>PMID:8462098</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/a3/2a36_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=2a36 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The N-terminal SH3 domain of the Drosophila adapter protein Drk (drkN SH3 domain) is marginally stable (DeltaG(U) = 1 kcal/mol) and exists in equilibrium between folded and highly populated unfolded states. The single substitution T22G, however, completely stabilizes the protein (DeltaG(U) = 4.0 kcal/mol). To probe the causes of instability of the wild-type (WT) protein and the dramatic stabilization of the mutant, we determined and compared nuclear magnetic resonance structures of the folded WT and mutant drkN SH3 domains. Residual dipolar coupling (RDC) and carbonyl chemical-shift anisotropy (C'-CSA) restraints measured for the WT and T22G domains were used for calculating the structures. The structures for the WT and mutant are highly similar. Thr22 of the WT and Gly22 of the mutant are at the i + 2 position of the diverging, type-II beta-turn. Interestingly, not only Gly22 but also Thr22 successfully adopt an alpha(L) conformation, required at this position of the turn, despite the fact that positive phi values are energetically unfavorable and normally disallowed for threonine residues. Forcing the Thr22 residue into this unnatural conformation increases the free energy of the folded state of the WT domain relative to its T22G mutant. Evidence for residual helix formation in the diverging turn region has been previously reported for the unfolded state of the WT drkN SH3 domain, and this, in addition to other residual structure, has been proposed to play a role in decreasing the free energy of the unfolded state of the protein. Together these data provide evidence that both increasing the free energy of the folded state and decreasing the free energy of the unfolded state of the protein contribute to instability of the WT drkN SH3 domain.

Structural comparison of the unstable drkN SH3 domain and a stable mutant.,Bezsonova I, Singer A, Choy WY, Tollinger M, Forman-Kay JD Biochemistry. 2005 Nov 29;44(47):15550-60. PMID:16300404<ref>PMID:16300404</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2a36" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Bezsonova I]]
[[Category: Choy W-Y]]
[[Category: Forman-Kay JD]]
[[Category: Singer A]]
[[Category: Tollinger M]]