This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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
| |||||||||||
