4a24

From Proteopedia

(Difference between revisions)

Current revision

Structural and functional analysis of the DEAF-1 and BS69 MYND domains

Structural highlights

4a24 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DEAF1_HUMAN Transcription factor that binds to sequence with multiple copies of 5'-TTC[CG]G-3' present in its own promoter and that of the HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to the retinoic acid response element (RARE) 5'-AGGGTTCACCGAAAGTTCA-3'. Activates the proenkephalin gene independently of promoter binding, probably through protein-protein interaction. When secreted, behaves as an inhibitor of cell proliferation, by arresting cells in the G0 or G1 phase. Required for neural tube closure and skeletal patterning. Regulates epithelial cell proliferation and side-branching in the mammary gland. Controls the expression of peripheral tissue antigens in pancreatic lymph nodes. Isoform 1 displays greater transcriptional activity than isoform 4. Isoform 4 may inhibit transcriptional activity of isoform 1 by interacting with isoform 1 and retaining it in the cytoplasm.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

DEAF-1 is an important transcriptional regulator that is required for embryonic development and is linked to clinical depression and suicidal behavior in humans. It comprises various structural domains, including a SAND domain that mediates DNA binding and a MYND domain, a cysteine-rich module organized in a Cys(4)-Cys(2)-His-Cys (C4-C2HC) tandem zinc binding motif. DEAF-1 transcription regulation activity is mediated through interactions with cofactors such as NCoR and SMRT. Despite the important biological role of the DEAF-1 protein, little is known regarding the structure and binding properties of its MYND domain.Here, we report the solution structure, dynamics and ligand binding of the human DEAF-1 MYND domain encompassing residues 501-544 determined by NMR spectroscopy. The structure adopts a betabetaalpha fold that exhibits tandem zinc-binding sites with a cross-brace topology, similar to the MYND domains in AML1/ETO and other proteins. We show that the DEAF-1 MYND domain binds to peptides derived from SMRT and NCoR corepressors. The binding surface mapped by NMR titrations is similar to the one previously reported for AML1/ETO. The ligand binding and molecular functions of the related BS69 MYND domain were studied based on a homology model and mutational analysis. Interestingly, the interaction between BS69 and its binding partners (viral and cellular proteins) seems to require distinct charged residues flanking the predicted MYND domain fold, suggesting a different binding mode. Our findings demonstrate that the MYND domain is a conserved zinc binding fold that plays important roles in transcriptional regulation by mediating distinct molecular interactions with viral and cellular proteins.

Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains.,Kateb F, Perrin H, Tripsianes K, Zou P, Spadaccini R, Bottomley M, Franzmann TM, Buchner J, Ansieau S, Sattler M PLoS One. 2013;8(1):e54715. doi: 10.1371/journal.pone.0054715. Epub 2013 Jan 25. PMID:23372760^[6]

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

References

↑ Manne U, Gary BD, Oelschlager DK, Weiss HL, Frost AR, Grizzle WE. Altered subcellular localization of suppressin, a novel inhibitor of cell-cycle entry, is an independent prognostic factor in colorectal adenocarcinomas. Clin Cancer Res. 2001 Nov;7(11):3495-503. PMID:11705868
↑ Yip L, Su L, Sheng D, Chang P, Atkinson M, Czesak M, Albert PR, Collier AR, Turley SJ, Fathman CG, Creusot RJ. Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes. Nat Immunol. 2009 Sep;10(9):1026-33. doi: 10.1038/ni.1773. Epub 2009 Aug 9. PMID:19668219 doi:10.1038/ni.1773
↑ Michelson RJ, Collard MW, Ziemba AJ, Persinger J, Bartholomew B, Huggenvik JI. Nuclear DEAF-1-related (NUDR) protein contains a novel DNA binding domain and represses transcription of the heterogeneous nuclear ribonucleoprotein A2/B1 promoter. J Biol Chem. 1999 Oct 22;274(43):30510-9. PMID:10521432
↑ Bottomley MJ, Collard MW, Huggenvik JI, Liu Z, Gibson TJ, Sattler M. The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. Nat Struct Biol. 2001 Jul;8(7):626-33. PMID:11427895 doi:http://dx.doi.org/10.1038/89675
↑ Barker HE, Smyth GK, Wettenhall J, Ward TA, Bath ML, Lindeman GJ, Visvader JE. Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary gland. BMC Dev Biol. 2008 Oct 1;8:94. doi: 10.1186/1471-213X-8-94. PMID:18826651 doi:10.1186/1471-213X-8-94
↑ Kateb F, Perrin H, Tripsianes K, Zou P, Spadaccini R, Bottomley M, Franzmann TM, Buchner J, Ansieau S, Sattler M. Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains. PLoS One. 2013;8(1):e54715. doi: 10.1371/journal.pone.0054715. Epub 2013 Jan 25. PMID:23372760 doi:http://dx.doi.org/10.1371/journal.pone.0054715

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4a24"

@@ Line 1: / Line 1: @@
 ==Structural and functional analysis of the DEAF-1 and BS69 MYND domains==
-<StructureSection load='4a24' size='340' side='right' caption='[[4a24]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='4a24' size='340' side='right'caption='[[4a24]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4a24]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A24 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A24 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4a24]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A24 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=4a24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a24 OCA], [http://pdbe.org/4a24 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a24 RCSB], [http://www.ebi.ac.uk/pdbsum/4a24 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a24 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4a24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a24 OCA], [https://pdbe.org/4a24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a24 RCSB], [https://www.ebi.ac.uk/pdbsum/4a24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a24 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DEAF1_HUMAN DEAF1_HUMAN]] Transcription factor that binds to sequence with multiple copies of 5'-TTC[CG]G-3' present in its own promoter and that of the HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to the retinoic acid response element (RARE) 5'-AGGGTTCACCGAAAGTTCA-3'. Activates the proenkephalin gene independently of promoter binding, probably through protein-protein interaction. When secreted, behaves as an inhibitor of cell proliferation, by arresting cells in the G0 or G1 phase. Required for neural tube closure and skeletal patterning. Regulates epithelial cell proliferation and side-branching in the mammary gland. Controls the expression of peripheral tissue antigens in pancreatic lymph nodes. Isoform 1 displays greater transcriptional activity than isoform 4. Isoform 4 may inhibit transcriptional activity of isoform 1 by interacting with isoform 1 and retaining it in the cytoplasm.<ref>PMID:11705868</ref> <ref>PMID:19668219</ref> <ref>PMID:10521432</ref> <ref>PMID:11427895</ref> <ref>PMID:18826651</ref>
+[https://www.uniprot.org/uniprot/DEAF1_HUMAN DEAF1_HUMAN] Transcription factor that binds to sequence with multiple copies of 5'-TTC[CG]G-3' present in its own promoter and that of the HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to the retinoic acid response element (RARE) 5'-AGGGTTCACCGAAAGTTCA-3'. Activates the proenkephalin gene independently of promoter binding, probably through protein-protein interaction. When secreted, behaves as an inhibitor of cell proliferation, by arresting cells in the G0 or G1 phase. Required for neural tube closure and skeletal patterning. Regulates epithelial cell proliferation and side-branching in the mammary gland. Controls the expression of peripheral tissue antigens in pancreatic lymph nodes. Isoform 1 displays greater transcriptional activity than isoform 4. Isoform 4 may inhibit transcriptional activity of isoform 1 by interacting with isoform 1 and retaining it in the cytoplasm.<ref>PMID:11705868</ref> <ref>PMID:19668219</ref> <ref>PMID:10521432</ref> <ref>PMID:11427895</ref> <ref>PMID:18826651</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Ansieau, S]]
+[[Category: Large Structures]]
-[[Category: Bepperling, A]]
+[[Category: Ansieau S]]
-[[Category: Bottomley, M]]
+[[Category: Bepperling A]]
-[[Category: Kateb, F]]
+[[Category: Bottomley M]]
-[[Category: Perrin, H]]
+[[Category: Kateb F]]
-[[Category: Sattler, M]]
+[[Category: Perrin H]]
-[[Category: Spadaccini, R]]
+[[Category: Sattler M]]
-[[Category: Tripsianes, K]]
+[[Category: Spadaccini R]]
-[[Category: Zou, P]]
+[[Category: Tripsianes K]]
-[[Category: Protein binding]]
+[[Category: Zou P]]
-[[Category: Transcription]]
-[[Category: Transcriptional regulation]]
-[[Category: Zinc-binding]]

4a24

From Proteopedia

Current revision

Structural and functional analysis of the DEAF-1 and BS69 MYND domains

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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