2wp2: Difference between revisions

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<StructureSection load='2wp2' size='340' side='right'caption='[[2wp2]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
<StructureSection load='2wp2' size='340' side='right'caption='[[2wp2]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2wp2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WP2 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2wp2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WP2 FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.37&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1u35|1u35]], [[1f66|1f66]], [[2wp1|2wp1]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</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=2wp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wp2 OCA], [https://pdbe.org/2wp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wp2 RCSB], [https://www.ebi.ac.uk/pdbsum/2wp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wp2 ProSAT]</span></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=2wp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wp2 OCA], [https://pdbe.org/2wp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wp2 RCSB], [https://www.ebi.ac.uk/pdbsum/2wp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wp2 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/BRDT_MOUSE BRDT_MOUSE]] Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.<ref>PMID:12861021</ref> <ref>PMID:22901802</ref> <ref>PMID:22922464</ref> <ref>PMID:22570411</ref> <ref>PMID:19794495</ref>
[https://www.uniprot.org/uniprot/BRDT_MOUSE BRDT_MOUSE] Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.<ref>PMID:12861021</ref> <ref>PMID:22901802</ref> <ref>PMID:22922464</ref> <ref>PMID:22570411</ref> <ref>PMID:19794495</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wp2 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wp2 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A key step in many chromatin-related processes is the recognition of histone post-translational modifications by effector modules such as bromodomains and chromo-like domains of the Royal family. Whereas effector-mediated recognition of single post-translational modifications is well characterized, how the cell achieves combinatorial readout of histones bearing multiple modifications is poorly understood. One mechanism involves multivalent binding by linked effector modules. For example, the tandem bromodomains of human TATA-binding protein-associated factor-1 (TAF1) bind better to a diacetylated histone H4 tail than to monoacetylated tails, a cooperative effect attributed to each bromodomain engaging one acetyl-lysine mark. Here we report a distinct mechanism of combinatorial readout for the mouse TAF1 homologue Brdt, a testis-specific member of the BET protein family. Brdt associates with hyperacetylated histone H4 (ref. 7) and is implicated in the marked chromatin remodelling that follows histone hyperacetylation during spermiogenesis, the stage of spermatogenesis in which post-meiotic germ cells mature into fully differentiated sperm. Notably, we find that a single bromodomain (BD1) of Brdt is responsible for selectively recognizing histone H4 tails bearing two or more acetylation marks. The crystal structure of BD1 bound to a diacetylated H4 tail shows how two acetyl-lysine residues cooperate to interact with one binding pocket. Structure-based mutagenesis that reduces the selectivity of BD1 towards diacetylated tails destabilizes the association of Brdt with acetylated chromatin in vivo. Structural analysis suggests that other chromatin-associated proteins may be capable of a similar mode of ligand recognition, including yeast Bdf1, human TAF1 and human CBP/p300 (also known as CREBBP and EP300, respectively). Our findings describe a new mechanism for the combinatorial readout of histone modifications in which a single effector module engages two marks on a histone tail as a composite binding epitope.
Cooperative binding of two acetylation marks on a histone tail by a single bromodomain.,Moriniere J, Rousseaux S, Steuerwald U, Soler-Lopez M, Curtet S, Vitte AL, Govin J, Gaucher J, Sadoul K, Hart DJ, Krijgsveld J, Khochbin S, Muller CW, Petosa C Nature. 2009 Oct 1;461(7264):664-8. PMID:19794495<ref>PMID:19794495</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2wp2" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Curtet, S]]
[[Category: Curtet S]]
[[Category: Gaucher, J]]
[[Category: Gaucher J]]
[[Category: Govin, J]]
[[Category: Govin J]]
[[Category: Hart, D J]]
[[Category: Hart DJ]]
[[Category: Khochbin, S]]
[[Category: Khochbin S]]
[[Category: Krijgsveld, J]]
[[Category: Krijgsveld J]]
[[Category: Moriniere, J]]
[[Category: Moriniere J]]
[[Category: Mueller, C W]]
[[Category: Mueller CW]]
[[Category: Petosa, C]]
[[Category: Petosa C]]
[[Category: Rousseaux, S]]
[[Category: Rousseaux S]]
[[Category: Sadoul, K]]
[[Category: Sadoul K]]
[[Category: Soler-Lopez, M]]
[[Category: Soler-Lopez M]]
[[Category: Steuerwald, U]]
[[Category: Steuerwald U]]
[[Category: Vitte, A L]]
[[Category: Vitte A-L]]
[[Category: Acetyllysine]]
[[Category: Brdt]]
[[Category: Chromosomal protein]]
[[Category: Coiled coil]]
[[Category: Nucleosome]]
[[Category: Nucleus]]
[[Category: Transcription regulation]]
[[Category: Transcription-peptide complex]]

Latest revision as of 10:10, 1 May 2024

Structure of Brdt bromodomain BD1 bound to a diacetylated histone H4 peptide.Structure of Brdt bromodomain BD1 bound to a diacetylated histone H4 peptide.

Structural highlights

2wp2 is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.37Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BRDT_MOUSE Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.[1] [2] [3] [4] [5]

Evolutionary Conservation

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

References

  1. ↑ Pivot-Pajot C, Caron C, Govin J, Vion A, Rousseaux S, Khochbin S. Acetylation-dependent chromatin reorganization by BRDT, a testis-specific bromodomain-containing protein. Mol Cell Biol. 2003 Aug;23(15):5354-65. PMID:12861021
  2. ↑ Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE. Small-Molecule Inhibition of BRDT for Male Contraception. Cell. 2012 Aug 17;150(4):673-684. PMID:22901802 doi:10.1016/j.cell.2012.06.045
  3. ↑ Gaucher J, Boussouar F, Montellier E, Curtet S, Buchou T, Bertrand S, Hery P, Jounier S, Depaux A, Vitte AL, Guardiola P, Pernet K, Debernardi A, Lopez F, Holota H, Imbert J, Wolgemuth DJ, Gerard M, Rousseaux S, Khochbin S. Bromodomain-dependent stage-specific male genome programming by Brdt. EMBO J. 2012 Oct 3;31(19):3809-20. doi: 10.1038/emboj.2012.233. Epub 2012 Aug 24. PMID:22922464 doi:http://dx.doi.org/10.1038/emboj.2012.233
  4. ↑ Berkovits BD, Wang L, Guarnieri P, Wolgemuth DJ. The testis-specific double bromodomain-containing protein BRDT forms a complex with multiple spliceosome components and is required for mRNA splicing and 3'-UTR truncation in round spermatids. Nucleic Acids Res. 2012 Aug;40(15):7162-75. doi: 10.1093/nar/gks342. Epub 2012, May 8. PMID:22570411 doi:http://dx.doi.org/10.1093/nar/gks342
  5. ↑ Moriniere J, Rousseaux S, Steuerwald U, Soler-Lopez M, Curtet S, Vitte AL, Govin J, Gaucher J, Sadoul K, Hart DJ, Krijgsveld J, Khochbin S, Muller CW, Petosa C. Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature. 2009 Oct 1;461(7264):664-8. PMID:19794495 doi:nature08397

2wp2, resolution 2.37Å

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