14-3-3 protein: Difference between revisions

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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-<StructureSection load='3smk' size='340' side='right' caption='Structure of human 14-3-3 protein σ complex with TASK-3 peptide and stabilizer (PDB code [[3smk]]).' scene=''>
+<StructureSection load='' size='340' side='right' caption='Structure of human 14-3-3 protein ζ with phosphopeptide (yellow) (PDB code [[1qja]]).' scene='59/590827/Cv/11'>
-== Function ==
-'''14-3-3 proteins''' (PRS) are conserved regulatory proteins which bind to a multitude of signaling proteins like kinases phosphatases and transmembrane receptors.  The name 14-3-3 derives from their elution pattern via chromatography.
+== Introduction ==
+The '''14-3-3 proteins''' (PRS) are a family of highly conserved regulatory proteins found in all eukaryotic organisms. They are involved in diverse cellular processes, including signal transduction, cell cycle control, protein trafficking, apoptosis (programmed cell death), and various other regulatory functions. The name "14-3-3" refers to the initial method used to identify and separate these proteins based on their migration pattern during gel electrophoresis. The proteins migrate at approximately 30 kDa, giving the impression of a molecular weight of 14-3-3 <ref>PMID:15857576</ref>
-== Disease ==
+== Function ==
+One of the key features of 14-3-3 proteins is their ability to interact with a wide range of target proteins, often through phosphorylation-dependent mechanisms. They typically bind to target proteins that contain a specific phosphoserine or phosphothreonine motif. This interaction can alter the target protein's activity, stability, subcellular localization, or protein-protein interactions, thereby influencing various cellular processes.
-Elevated levels of PRS are found in patients with Creutzfeld-Jakob disease.
+The binding of 14-3-3 proteins to their target proteins can have diverse functional outcomes. It can either activate or inhibit the target protein, modulate its interactions with other proteins, protect it from degradation, or act as a scaffold for protein complex formation. By regulating the activity and localization of their target proteins, 14-3-3 proteins exert tight control over cellular signaling and contribute to the coordination of complex cellular processes.
-== Relevance ==
+These proteins are highly context-dependent and vary depending on the specific isoform, cellular location, and interacting partners. They have been implicated in numerous physiological and pathological processes, including neuronal development and function, cell cycle regulation, apoptosis, cancer progression, and neurodegenerative diseases.
-== Structural highlights ==
+Research on 14-3-3 proteins continues to uncover their intricate roles in cellular signaling and their involvement in various diseases. Understanding their interactions and regulatory mechanisms provides insights into fundamental cellular processes and offers potential avenues for therapeutic interventions.
-==3D structures of 14-3-3 proteins==
+== Disease ==
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+Elevated levels of PRS are found in patients with Creutzfeld-Jakob disease (CJD).  PRS are associated with Parkinson Disease (PD) and with Alzheimer Disease (AD) based on their localization and their binding to PD and AD-associated proteins.
-'''14-3-3 protein σ'''
+== Relevance ==
-[[1yz5]] – hPRS – human<br />
+PRS are tested as biomarkers for CJD, PD and AD.
-''14-3-3 protein σ binary complex with peptide''
+== Structural highlights ==
-[[1ywt]] – hPRS + phosphopeptide <br />
-[[3lw1]] – hPRS + p53 peptide <br />
-[[3iqj]], [[3iqu]], [[4iea]] – hPRS + Raf-1 peptide <br />
-[[3mhr]] – hPRS + YAP peptide <br />
-[[3p1n]] – hPRS + TASK-3 peptide <br />
-[[3p1p]], [[3p1r]] – hPRS (mutant) + TASK-3 peptide <br />
-[[4dat]], [[4dau]] – hPRS + PADI6 peptide <br />
-[[4jc3]], [[4jdd]] – hPRS + estrogen receptor peptide <br />
-[[4fl5]] – hPRS + τ protein peptide <br />
-''14-3-3 protein σ binary complex with small molecule''
-[[3u9x]] – hPRS + pyridoxal phosphate<br />
-[[3t0l]], [[3t0m]], [[4dhm]], [[4dhn]], [[4dho]], [[4dhp]], [[4dhq]], [[4dhr]], [[4dhs]], [[4dht]], [[4dhu]] – hPRS + inhibitor<br />
-[[4hqw]], [[4hru]] – hPRS + molecular tweezers<br />
-''14-3-3 protein σ ternary complex with stabilizer''
-[[3p1o]], [[3ux0]], [[4fr3]] – hPRS + TASK-3 peptide + stabilizer<br />
-[[3p1q]], [[3p1s]], [[3spr]], [[3smk]], [[3sml]], [[3smm]], [[3smn]], [[3smo]] – hPRS (mutant) + TASK-3 peptide + stabilizer<br />
-[[3iqv]], [[3o8i]] – hPRS + Raf-1 peptide + stabilizer<br />
-'''14-3-3 protein ζ'''
-[[1a4o]] – bPRS - bovine<br />
-[[1a37]] – bPRS + Raf peptide <br />
-[[1a38]] – bPRS + R18 peptide <br />
-'''14-3-3 protein ζ/δ'''
-[[3rdh]] – hPRS  <br />
-[[1qja]], [[1qjb]] – hPRS + phosphopeptide <br />
-[[2c1j]], [[2c1n]] – hPRS + histone H3 peptide <br />
-[[2o02]], [[4n7g]], [[4n7y]], [[4n84]] – hPRS + exoenzyme S peptide <br />
-[[2v7d]], [[4hkc]] – hPRS + integrin peptide <br />
-[[3cu8]], [[3nkx]], [[4fj3]], [[4ihl]] – hPRS + Raf-1 peptide <br />
-[[2wh0]] – hPRS + protein kinase C ε peptide <br />
-[[4bg6]] – hPRS + RND3 peptide <br />
-[[1ib1]] – hPRS + serotonin N-acetyltransferase <br />
-'''14-3-3 protein γ'''
-[[4e2e]] – hPRS  <br />
-[[2b05]] – hPRS + phosphopeptide <br />
-[[3uzd]] – hPRS + histone deacylase peptide <br />
-[[4j6s]] – hPRS + tyrosine hydroxylase peptide <br />
-[[4o46]] – hPRS + influenza C-terminal peptide <br />
-'''14-3-3 protein β/α'''
-[[2bq0]], [[2dnk]] – hPRS  <br />
-[[2c23]] – hPRS + exoenzyme S peptide <br />
-[[4gnt]] – PRS + CHREBP peptide - mouse<br />
-'''14-3-3 protein θ'''
-[[2btp]] – hPRS + phosphopeptide <br />
-'''14-3-3 protein η'''
+PRS are homo- and heterodimers containing <scene name='59/590827/Cv/14'>9 antiparallel α-helices</scene>. Three of the helices form the <scene name='59/590827/Cv/15'>dimerization domain</scene> (<font color='red'><b>3 helices of chain A are in red</b></font> and <font color='magenta'><b>3 helices of chain B are in magenta</b></font>). <scene name='59/590827/Cv/16'>Five residues (in PRS-σ and PRS-ζ) are involved in ligand binding</scene>.
-[[2c63]], [[2c74]] – hPRS + phosphopeptide <br />
+== 3D structures of 14-3-3 protein ==
-'''14-3-3 protein ε'''
+[[14-3-3 protein 3D structures]]
-[[2br9]] – hPRS + phosphopeptide <br />
+</StructureSection>
-[[3ual]], [[3ubw]] – hPRS + myeloid leukemia factor 1 peptide <br />