1h9d
From Proteopedia
(New page: 200px<br /> <applet load="1h9d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h9d, resolution 2.60Å" /> '''AML1/CBF-BETA/DNA C...) |
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| - | [[Image:1h9d.gif|left|200px]]<br /> | + | [[Image:1h9d.gif|left|200px]]<br /><applet load="1h9d" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1h9d" size=" | + | |
caption="1h9d, resolution 2.60Å" /> | caption="1h9d, resolution 2.60Å" /> | ||
'''AML1/CBF-BETA/DNA COMPLEX'''<br /> | '''AML1/CBF-BETA/DNA COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have determined the structure, at 2.6 A resolution, of the AML1 (Runx1) | + | We have determined the structure, at 2.6 A resolution, of the AML1 (Runx1) Runt domain--CBF beta--DNA ternary complex, the most common target for mutations in human leukemia. The structure reveals that the Runt domain DNA binding mechanism is unique within the p53 family of transcription factors. The extended C-terminal 'tail' and 'wing' elements adopt a specific DNA-bound conformation that clamps the phosphate backbone between the major and minor grooves of the distorted B-form DNA recognition site. Furthermore, the extended 'tail' mediates most of the NF-kappa B/Rel-like base-specific contacts in the major groove. The structure clearly explains the molecular basis for the loss of DNA binding function of the Runt domain--CBF beta complex as a consequence of the human disease-associated mutations in leukemogenesis and cleidocranial dysplasia. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1H9D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1H9D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H9D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bravo, J.]] | [[Category: Bravo, J.]] | ||
| - | [[Category: Warren, A | + | [[Category: Warren, A J.]] |
[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:57 2008'' |
Revision as of 10:58, 21 February 2008
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AML1/CBF-BETA/DNA COMPLEX
Contents |
Overview
We have determined the structure, at 2.6 A resolution, of the AML1 (Runx1) Runt domain--CBF beta--DNA ternary complex, the most common target for mutations in human leukemia. The structure reveals that the Runt domain DNA binding mechanism is unique within the p53 family of transcription factors. The extended C-terminal 'tail' and 'wing' elements adopt a specific DNA-bound conformation that clamps the phosphate backbone between the major and minor grooves of the distorted B-form DNA recognition site. Furthermore, the extended 'tail' mediates most of the NF-kappa B/Rel-like base-specific contacts in the major groove. The structure clearly explains the molecular basis for the loss of DNA binding function of the Runt domain--CBF beta complex as a consequence of the human disease-associated mutations in leukemogenesis and cleidocranial dysplasia.
Disease
Known diseases associated with this structure: Leukemia, acute myeloid OMIM:[151385], Myeloid leukemia, acute, M4Eo subtype OMIM:[121360], Platelet disorder, familial, with associated myeloid malignancy OMIM:[151385], Rheumatoid arthritis, susceptibility to OMIM:[151385]
About this Structure
1H9D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The leukemia-associated AML1 (Runx1)--CBF beta complex functions as a DNA-induced molecular clamp., Bravo J, Li Z, Speck NA, Warren AJ, Nat Struct Biol. 2001 Apr;8(4):371-8. PMID:11276260
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