7q16
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Human 14-3-3 zeta fused to the BAD peptide including phosphoserine-74== | ==Human 14-3-3 zeta fused to the BAD peptide including phosphoserine-74== | ||
| - | <StructureSection load='7q16' size='340' side='right'caption='[[7q16]]' scene=''> | + | <StructureSection load='7q16' size='340' side='right'caption='[[7q16]], [[Resolution|resolution]] 2.36Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q16 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q16 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7q16]] 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=7Q16 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q16 FirstGlance]. <br> |
| - | </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=7q16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q16 OCA], [https://pdbe.org/7q16 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q16 RCSB], [https://www.ebi.ac.uk/pdbsum/7q16 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q16 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=7q16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q16 OCA], [https://pdbe.org/7q16 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q16 RCSB], [https://www.ebi.ac.uk/pdbsum/7q16 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q16 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_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.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> [https://www.uniprot.org/uniprot/BAD_HUMAN BAD_HUMAN] Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Several signaling pathways control phosphorylation of the proapoptotic protein BAD and its phosphorylation-dependent association with 14-3-3 proteins in the cytoplasm. The stability of the 14-3-3/BAD complex determines the cell fate: unphosphorylated BAD escapes from 14-3-3, migrates to the mitochondria and initiates apoptosis. While the 14-3-3/BAD interaction represents a promising drug target, it lacks structural characterization. Among several phosphosites identified in vivo, Ser75 and Ser99 of human BAD match the consensus sequence RXXpSXP recognized by 14-3-3 and, therefore, represent canonical 14-3-3-binding sites. Yet, BAD contains other serines phosphorylatable in vivo, whose role is less understood. Here, we report a 2.36 A crystal structure of 14-3-3zeta complexed with a BAD fragment which includes residues Ser74 and Ser75, both being substrates for protein kinases. While the BAD peptide is anchored to 14-3-3 by phosphoserine as expected, the BAD peptide was unexpectedly phosphorylated at Ser74 instead of Ser75, revealing noncanonical binding within the amphipathic groove and leading to a one-step positional shift and reorganization of the interface. This observation exemplifies plasticity of the amphipathic 14-3-3 groove in accommodating various peptides and suggests the redundancy of Ser74 and Ser75 phosphosites with respect to binding of BAD to 14-3-3. | ||
| + | |||
| + | Crystal structure of human 14-3-3zeta complexed with the noncanonical phosphopeptide from proapoptotic BAD.,Sluchanko NN, Tugaeva KV, Gushchin I, Remeeva A, Kovalev K, Cooley RB Biochem Biophys Res Commun. 2021 Oct 26;583:100-105. doi:, 10.1016/j.bbrc.2021.10.053. PMID:34735870<ref>PMID:34735870</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7q16" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cooley RB]] | [[Category: Cooley RB]] | ||
Revision as of 06:24, 26 October 2022
Human 14-3-3 zeta fused to the BAD peptide including phosphoserine-74
| |||||||||||
