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1tot

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Revision as of 08:51, 21 March 2018

ZZ Domain of CBP- a Novel Fold for a Protein Interaction Module

Structural highlights

1tot is a 1 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1f81
Gene:	CREBBP, CBP (LK3 transgenic mice)
Activity:	Histone acetyltransferase, with EC number 2.3.1.48
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CBP_MOUSE] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (By similarity).^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

CREB-binding protein (CBP) is a large, multi-domain protein that provides a multitude of binding sites for transcriptional coactivators. The site of interaction of the tumor suppressor p53 and the oncoprotein E1A with CBP/p300 has been identified with the third cysteine-histidine-rich (CH3) domain, which incorporates two zinc-binding motifs, ZZ and TAZ2. We show that these two domains fold independently and do not interact in solution. Our experiments demonstrate conclusively that the interaction of p53 and E1A with the CH3 domain resides exclusively in the TAZ2 domain, with no contribution from the ZZ domain. We report also the three-dimensional solution structure of the ZZ domain of murine CBP. The 52 residue ZZ domain contains two twisted antiparallel beta-sheets and a short alpha-helix, and binds two zinc ions. The identity of the zinc coordinating ligands was resolved unambiguously using NMR spectroscopy of the ZZ domain substituted with (113)Cd. One zinc ion is coordinated tetrahedrally via two CXXC motifs to four cysteine side-chains, and the second zinc ion is coordinated tetrahedrally by a third CXXC motif, together with an unusual HXH motif coordinating via the N(epsilon2) atom of His40 and the N(delta1) atom of His-42. The first zinc cluster of the ZZ domain is strictly conserved, whereas the second zinc cluster shows variability in the position of the two histidine residues, reflecting the wide variety of molecules that incorporate ZZ domains. The structure of the ZZ domain shows that it belongs to the family of cross-brace zinc finger motifs that include the PHD, RING, and FYVE domains; however, its biological function is unclear. Mapping of the positions of conserved residues onto the calculated structures reveals a face containing exposed aromatic and hydrophobic side-chains, while the opposite face contains a series of conserved charged or hydrophilic groups. These homologies suggest that the ZZ domain is involved in ligand binding or molecular scaffolding, with specificity provided by the variability of the sequence that contains the helix in the murine CPB ZZ domain structure.

ZZ domain of CBP: an unusual zinc finger fold in a protein interaction module.,Legge GB, Martinez-Yamout MA, Hambly DM, Trinh T, Lee BM, Dyson HJ, Wright PE J Mol Biol. 2004 Oct 29;343(4):1081-93. PMID:15476823^[5]

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

References

↑ Hung HL, Lau J, Kim AY, Weiss MJ, Blobel GA. CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites. Mol Cell Biol. 1999 May;19(5):3496-505. PMID:10207073
↑ Xu W, Chen H, Du K, Asahara H, Tini M, Emerson BM, Montminy M, Evans RM. A transcriptional switch mediated by cofactor methylation. Science. 2001 Dec 21;294(5551):2507-11. Epub 2001 Nov 8. PMID:11701890 doi:10.1126/science.1065961
↑ Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, Nakajima T, Fukamizu A. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10042-7. Epub 2004 Jun 25. PMID:15220471 doi:10.1073/pnas.0400593101
↑ Kuo HY, Chang CC, Jeng JC, Hu HM, Lin DY, Maul GG, Kwok RP, Shih HM. SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):16973-8. Epub 2005 Nov 15. PMID:16287980 doi:10.1073/pnas.0504460102
↑ Legge GB, Martinez-Yamout MA, Hambly DM, Trinh T, Lee BM, Dyson HJ, Wright PE. ZZ domain of CBP: an unusual zinc finger fold in a protein interaction module. J Mol Biol. 2004 Oct 29;343(4):1081-93. PMID:15476823 doi:10.1016/j.jmb.2004.08.087

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1tot"

@@ Line 1: / Line 1: @@
 ==ZZ Domain of CBP- a Novel Fold for a Protein Interaction Module==
 <StructureSection load='1tot' size='340' side='right' caption='[[1tot]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CREBBP, CBP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=1tot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tot OCA], [http://pdbe.org/1tot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tot RCSB], [http://www.ebi.ac.uk/pdbsum/1tot 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=1tot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tot OCA], [http://pdbe.org/1tot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tot RCSB], [http://www.ebi.ac.uk/pdbsum/1tot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tot ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/to/1tot_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/to/1tot_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1tot

From Proteopedia

Revision as of 08:51, 21 March 2018

ZZ Domain of CBP- a Novel Fold for a Protein Interaction Module

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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