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4hkc

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Revision as of 18:06, 5 August 2016

14-3-3-zeta in complex with S1011 phosphorylated integrin alpha-4 peptide

Structural highlights

4hkc is a 2 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:
Related:	2v7d
Gene:	YWHAZ (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] [ITA4_HUMAN] Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells.

Publication Abstract from PubMed

Integrins are a family of heterodimeric (alpha+beta) adhesion receptors that play key roles in many cellular processes. Integrins are unusual in that their functions can be modulated from both outside and inside the cell. Inside-out signaling is mediated by binding adaptor proteins to the flexible cytoplasmic tails of the alpha- and beta-integrin subunits. Talin is one well-known intracellular activator, but various other adaptors bind to integrin tails, including 14-3-3-zeta, a member of the 14-3-3 family of dimeric proteins that have a preference for binding phosphorylated sequence motifs. Phosphorylation of a threonine in the beta2 integrin tail has been shown to modulate beta2/14-3-3-zeta interactions, and recently, the alpha4 integrin tail was reported to bind to 14-3-3-zeta and associate with paxillin in a ternary complex that is regulated by serine phosphorylation. Here, we use a range of biophysical techniques to characterize interactions between 14-3-3-zeta and the cytoplasmic tails of alpha4, beta1, beta2 and beta3 integrins. The X-ray structure of the 14-3-3-zeta/alpha4 complex indicates a canonical binding mode for the alpha4 phospho-peptide, but unexpected features are also observed: residues outside the consensus 14-3-3-zeta binding motif are shown to be essential for an efficient interaction; in contrast, a short beta2 phospho-peptide is sufficient for high-affinity binding to 14-3-3-zeta. In addition, we report novel 14-3-3-zeta/integrin tail interactions that are independent of phosphorylation. Of the integrin tails studied, the strongest interaction with 14-3-3-zeta is observed for the beta1A variant. In summary, new insights about 14-3-3-zeta/integrin tail interactions that have implications for the role of these molecular associations in cells are described.

Characterization of 14-3-3-zeta Interactions with Integrin Tails.,Bonet R, Vakonakis I, Campbell ID J Mol Biol. 2013 Jun 11. pii: S0022-2836(13)00354-9. doi:, 10.1016/j.jmb.2013.05.024. PMID:23763993^[6]

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

References

↑ Dubois T, Rommel C, Howell S, Steinhussen U, Soneji Y, Morrice N, Moelling K, Aitken A. 14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction. J Biol Chem. 1997 Nov 14;272(46):28882-8. PMID:9360956
↑ Zheng W, Zhang Z, Ganguly S, Weller JL, Klein DC, Cole PA. Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. Nat Struct Biol. 2003 Dec;10(12):1054-7. Epub 2003 Oct 26. PMID:14578935 doi:10.1038/nsb1005
↑ Tsuruta F, Sunayama J, Mori Y, Hattori S, Shimizu S, Tsujimoto Y, Yoshioka K, Masuyama N, Gotoh Y. JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO J. 2004 Apr 21;23(8):1889-99. Epub 2004 Apr 8. PMID:15071501 doi:10.1038/sj.emboj.7600194
↑ Ganguly S, Weller JL, Ho A, Chemineau P, Malpaux B, Klein DC. Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1222-7. Epub 2005 Jan 11. PMID:15644438 doi:0406871102
↑ Gu YM, Jin YH, Choi JK, Baek KH, Yeo CY, Lee KY. Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon. FEBS Lett. 2006 Jan 9;580(1):305-10. Epub 2005 Dec 19. PMID:16376338 doi:S0014-5793(05)01485-7
↑ Bonet R, Vakonakis I, Campbell ID. Characterization of 14-3-3-zeta Interactions with Integrin Tails. J Mol Biol. 2013 Jun 11. pii: S0022-2836(13)00354-9. doi:, 10.1016/j.jmb.2013.05.024. PMID:23763993 doi:10.1016/j.jmb.2013.05.024

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/4hkc"

@@ Line 1: / Line 1: @@
 ==14-3-3-zeta in complex with S1011 phosphorylated integrin alpha-4 peptide==
 <StructureSection load='4hkc' size='340' side='right' caption='[[4hkc]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v7d|2v7d]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YWHAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hkc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hkc RCSB], [http://www.ebi.ac.uk/pdbsum/4hkc PDBsum]</span></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=4hkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hkc OCA], [http://pdbe.org/4hkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hkc RCSB], [http://www.ebi.ac.uk/pdbsum/4hkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hkc ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4hkc" style="background-color:#fffaf0;"></div>
 ==See Also==

4hkc

From Proteopedia

Revision as of 18:06, 5 August 2016

14-3-3-zeta in complex with S1011 phosphorylated integrin alpha-4 peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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