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6a5q

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Revision as of 06:31, 29 May 2019

Structure of 14-3-3 beta in complex with TFEB 14-3-3 binding motif

Structural highlights

6a5q is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	YWHAB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

Publication Abstract from PubMed

As a master regulator of the macroautophagy/autophagy-lysosomal pathway, TFEB (transcription factor EB) plays a prominent role in regulating neurodegenerative diseases and cancer. The transcription activity of TFEB is tightly controlled by phosphorylation and dephosphorylation. Phosphorylated S211 (p-S211) of TFEB can be recognized by YWHA/14-3-3 proteins for TFEB cytoplasmic localization. Here, we characterized the interactions between phosphorylated TFEB and YWHA/14-3-3 proteins and determined the structures of YWHA/14-3-3 proteins in complex with a TFEB p-S211-peptide. Although the critical arginine for YWHA/14-3-3 recognition is missing in the N terminus of the TFEB p-S211-peptide, the C-terminal additional hydrophobic residues of the peptide unexpectedly occupy nearly half of the target-binding groove of YWHA/14-3-3 proteins, which compensates for the N-terminal defect and is distinct from the canonical YWHA/14-3-3-binding mode. Mutations of essential residues in the interaction interface between TFEB and YWHA/14-3-3 proteins disrupted their interactions and severely impaired the cytoplasmic localization of TFEB, which altered the expression of TFEB target genes and affected autophagy. Thus, YWHA/14-3-3 proteins recognize phosphorylated TFEB by a noncanonical mode for controlling TFEB cytoplasmic localization and its activity. Abbreviation: ACTB: actin beta; ALP: autophagy-lysosomal pathway; ATP6V1H: ATPase H(+) transporting V1 subunit H; bHLH: basic helix-loop-helix; CLEAR: coordinated lysosomal expression and regulation; Co-IP: co-immunoprecipitation; CTSB: cathepsin B; CTSD: cathepsin D; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MITF: melanocyte inducing transcription factor; NLS: nuclear localization signal; TFEB: transcription factor EB; YWHA/14-3-3: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein.

YWHA/14-3-3 proteins recognize phosphorylated TFEB by a noncanonical mode for controlling TFEB cytoplasmic localization.,Xu Y, Ren J, He X, Chen H, Wei T, Feng W Autophagy. 2019 Jan 17:1-14. doi: 10.1080/15548627.2019.1569928. PMID:30653408^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Liu Y, Ross JF, Bodine PV, Billiard J. Homodimerization of Ror2 tyrosine kinase receptor induces 14-3-3(beta) phosphorylation and promotes osteoblast differentiation and bone formation. Mol Endocrinol. 2007 Dec;21(12):3050-61. Epub 2007 Aug 23. PMID:17717073 doi:http://dx.doi.org/10.1210/me.2007-0323
↑ Jang SW, Liu X, Fu H, Rees H, Yepes M, Levey A, Ye K. Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons. J Biol Chem. 2009 Sep 4;284(36):24512-25. doi: 10.1074/jbc.M109.026237. Epub 2009, Jul 10. PMID:19592491 doi:10.1074/jbc.M109.026237
↑ Xu Y, Ren J, He X, Chen H, Wei T, Feng W. YWHA/14-3-3 proteins recognize phosphorylated TFEB by a noncanonical mode for controlling TFEB cytoplasmic localization. Autophagy. 2019 Jan 17:1-14. doi: 10.1080/15548627.2019.1569928. PMID:30653408 doi:http://dx.doi.org/10.1080/15548627.2019.1569928

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6a5q"

@@ Line 1: / Line 1: @@
 ==Structure of 14-3-3 beta in complex with TFEB 14-3-3 binding motif==
-<StructureSection load='6a5q' size='340' side='right' caption='[[6a5q]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='6a5q' size='340' side='right'caption='[[6a5q]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6a5q]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A5Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A5Q FirstGlance]. <br>
@@ Line 28: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Feng, W]]
 [[Category: Ren, J Q]]

6a5q

From Proteopedia

Revision as of 06:31, 29 May 2019

Structure of 14-3-3 beta in complex with TFEB 14-3-3 binding motif

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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