View source for 6gnn


==Exoenzyme T from Pseudomonas aeruginosa in complex with human 14-3-3 protein beta, tetrameric crystal form bound to STO1101==
<StructureSection load='6gnn' size='340' side='right' caption='[[6gnn]], [[Resolution|resolution]] 3.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gnn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GNN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GNN FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F4W:3-(12-oxidanylidene-7-thia-9,11-diazatricyclo[6.4.0.0^{2,6}]dodeca-1(8),2(6),9-trien-10-yl)propanoic+acid'>F4W</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gnn OCA], [http://pdbe.org/6gnn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gnn RCSB], [http://www.ebi.ac.uk/pdbsum/6gnn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gnn ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/1433B_HUMAN 1433B_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2.<ref>PMID:17717073</ref> <ref>PMID:19592491</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3beta:ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.

14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface.,Karlberg T, Hornyak P, Pinto AF, Milanova S, Ebrahimi M, Lindberg M, Pullen N, Nordstrom A, Loverli E, Caraballo R, Wong EV, Nareoja K, Thorsell AG, Elofsson M, De La Cruz EM, Bjorkegren C, Schuler H Nat Commun. 2018 Sep 17;9(1):3785. doi: 10.1038/s41467-018-06194-1. PMID:30224724<ref>PMID:30224724</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gnn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hornyak, P]]
[[Category: Karlberg, T]]
[[Category: Nareoja, K]]
[[Category: Pinto, A F]]
[[Category: Schuler, H]]
[[Category: Thorsell, A G]]
[[Category: Adp-ribosylation]]
[[Category: Exot]]
[[Category: Nad]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Toxin]]