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5naf

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Revision as of 12:00, 26 August 2020

Co-crystal structure of an MeCP2 peptide with TBLR1 WD40 domain

Structural highlights

5naf is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TBL1R_MOUSE] F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation (By similarity). [MECP2_MOUSE] Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC).^[1]

Publication Abstract from PubMed

Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin-beta like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.

Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders.,Kruusvee V, Lyst MJ, Taylor C, Tarnauskaite Z, Bird AP, Cook AG Proc Natl Acad Sci U S A. 2017 Mar 27. pii: 201700731. doi:, 10.1073/pnas.1700731114. PMID:28348241^[2]

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

References

↑ Spruijt CG, Gnerlich F, Smits AH, Pfaffeneder T, Jansen PW, Bauer C, Munzel M, Wagner M, Muller M, Khan F, Eberl HC, Mensinga A, Brinkman AB, Lephikov K, Muller U, Walter J, Boelens R, van Ingen H, Leonhardt H, Carell T, Vermeulen M. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Cell. 2013 Feb 28;152(5):1146-59. doi: 10.1016/j.cell.2013.02.004. Epub 2013 Feb , 21. PMID:23434322 doi:http://dx.doi.org/10.1016/j.cell.2013.02.004
↑ Kruusvee V, Lyst MJ, Taylor C, Tarnauskaite Z, Bird AP, Cook AG. Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders. Proc Natl Acad Sci U S A. 2017 Mar 27. pii: 201700731. doi:, 10.1073/pnas.1700731114. PMID:28348241 doi:http://dx.doi.org/10.1073/pnas.1700731114

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/5naf"

@@ Line 1: / Line 1: @@
 ==Co-crystal structure of an MeCP2 peptide with TBLR1 WD40 domain==
-<StructureSection load='5naf' size='340' side='right' caption='[[5naf]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
+<StructureSection load='5naf' size='340' side='right'caption='[[5naf]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5naf]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NAF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NAF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5naf]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NAF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NAF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5naf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5naf OCA], [http://pdbe.org/5naf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5naf RCSB], [http://www.ebi.ac.uk/pdbsum/5naf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5naf ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5naf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5naf OCA], [http://pdbe.org/5naf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5naf RCSB], [http://www.ebi.ac.uk/pdbsum/5naf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5naf ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Cook, A G]]
 [[Category: Kruusvee, V]]

5naf

From Proteopedia

Revision as of 12:00, 26 August 2020

Co-crystal structure of an MeCP2 peptide with TBLR1 WD40 domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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