1cs3
From Proteopedia
(New page: 200px<br /> <applet load="1cs3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cs3, resolution 2.00Å" /> '''STRUCTURE OF BTB/PO...) |
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| - | [[Image:1cs3.gif|left|200px]]<br /> | + | [[Image:1cs3.gif|left|200px]]<br /><applet load="1cs3" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1cs3" size=" | + | |
caption="1cs3, resolution 2.00Å" /> | caption="1cs3, resolution 2.00Å" /> | ||
'''STRUCTURE OF BTB/POZ TRANSCRIPTION REPRESSION DOMAIN FROM PROMELOCYTIC LEUKEMIA ZINC FINGER ONCOPROTEIN'''<br /> | '''STRUCTURE OF BTB/POZ TRANSCRIPTION REPRESSION DOMAIN FROM PROMELOCYTIC LEUKEMIA ZINC FINGER ONCOPROTEIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The evolutionarily conserved BTB/POZ domain from the promyelocytic | + | The evolutionarily conserved BTB/POZ domain from the promyelocytic leukemia zinc finger (PLZF) oncoprotein mediates transcriptional repression through the recruitment of corepressor proteins containing histone deacetylases in acute promyelocytic leukemia. We have determined the 2.0 A crystal structure of the BTB/POZ domain from PLZF (PLZF-BTB/POZ), and have carried out biochemical analysis of PLZF-BTB/POZ harboring site-directed mutations to probe structure-function relationships. The structure reveals a novel alpha/beta homodimeric fold in which dimer interactions occur along two surfaces of the protein subunits. The conservation of BTB/POZ domain residues at the core of the protomers and at the dimer interface implies an analogous fold and dimerization mode for BTB/POZ domains from otherwise functionally unrelated proteins. Unexpectedly, the BTB/POZ domain forms dimer-dimer interactions in the crystals, suggesting a mode for higher-order protein oligomerization for BTB/POZ-mediated transcriptional repression. Biochemical characterization of PLZF-BTB/POZ harboring mutations in conserved residues involved in protein dimerization reveals that the integrity of the dimer interface is exquisitely sensitive to mutation and that dimer formation is required for wild-type levels of transcriptional repression. Interestingly, similar mutational analysis of residues within a pronounced protein cleft along the dimer interface, which had been implicated previously for interaction with corepressors, has negligible effects on dimerization or transcriptional repression. Together, these studies form a structure-function framework for understanding BTB/POZ-mediated oligomerization and transcriptional repression properties. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1CS3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1CS3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CS3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: 3rd, F | + | [[Category: 3rd, F J.Rauscher.]] |
[[Category: Li, X.]] | [[Category: Li, X.]] | ||
[[Category: Marmorstein, R.]] | [[Category: Marmorstein, R.]] | ||
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[[Category: transcription repression]] | [[Category: transcription repression]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:09:09 2008'' |
Revision as of 10:09, 21 February 2008
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STRUCTURE OF BTB/POZ TRANSCRIPTION REPRESSION DOMAIN FROM PROMELOCYTIC LEUKEMIA ZINC FINGER ONCOPROTEIN
Contents |
Overview
The evolutionarily conserved BTB/POZ domain from the promyelocytic leukemia zinc finger (PLZF) oncoprotein mediates transcriptional repression through the recruitment of corepressor proteins containing histone deacetylases in acute promyelocytic leukemia. We have determined the 2.0 A crystal structure of the BTB/POZ domain from PLZF (PLZF-BTB/POZ), and have carried out biochemical analysis of PLZF-BTB/POZ harboring site-directed mutations to probe structure-function relationships. The structure reveals a novel alpha/beta homodimeric fold in which dimer interactions occur along two surfaces of the protein subunits. The conservation of BTB/POZ domain residues at the core of the protomers and at the dimer interface implies an analogous fold and dimerization mode for BTB/POZ domains from otherwise functionally unrelated proteins. Unexpectedly, the BTB/POZ domain forms dimer-dimer interactions in the crystals, suggesting a mode for higher-order protein oligomerization for BTB/POZ-mediated transcriptional repression. Biochemical characterization of PLZF-BTB/POZ harboring mutations in conserved residues involved in protein dimerization reveals that the integrity of the dimer interface is exquisitely sensitive to mutation and that dimer formation is required for wild-type levels of transcriptional repression. Interestingly, similar mutational analysis of residues within a pronounced protein cleft along the dimer interface, which had been implicated previously for interaction with corepressors, has negligible effects on dimerization or transcriptional repression. Together, these studies form a structure-function framework for understanding BTB/POZ-mediated oligomerization and transcriptional repression properties.
Disease
Known diseases associated with this structure: Leukemia, acute promyelocytic, PL2F/RARA type OMIM:[176797]
About this Structure
1CS3 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Structure-function studies of the BTB/POZ transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein., Li X, Peng H, Schultz DC, Lopez-Guisa JM, Rauscher FJ 3rd, Marmorstein R, Cancer Res. 1999 Oct 15;59(20):5275-82. PMID:10537309
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