1h9d | pdb_00001h9d
Aml1/cbf-beta/dna complex
Structural highlights
Disease[RUNX1_HUMAN] Note=A chromosomal aberration involving RUNX1/AML1 is a cause of M2 type acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1T1.[1] [2] [3] [4] [5] Note=A chromosomal aberration involving RUNX1/AML1 is a cause of therapy-related myelodysplastic syndrome (T-MDS). Translocation t(3;21)(q26;q22) with EAP or MECOM. Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with EAP or MECOM. Note=A chromosomal aberration involving RUNX1/AML1 is found in childhood acute lymphoblastic leukemia (ALL). Translocation t(12;21)(p13;q22) with TEL. The translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H. Note=A chromosomal aberration involving RUNX1 is found in acute leukemia. Translocation t(11,21)(q13;q22) that forms a MACROD1-RUNX1 fusion protein. Defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM) [MIM:601399]. FPDMM is an autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.[6] Note=A chromosomal aberration involving RUNX1/AML1 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein. Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelomonocytic leukemia. Inversion inv(21)(q21;q22) with USP16. [PEBB_HUMAN] Note=A chromosomal aberration involving CBFB is associated with acute myeloid leukemia of M4EO subtype. Pericentric inversion inv(16)(p13;q22). The inversion produces a fusion protein that consists of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11. Function[RUNX1_HUMAN] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. The alpha subunit binds DNA and appears to have a role in the development of normal hematopoiesis. Isoform AML-1L interferes with the transactivation activity of RUNX1. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the mouse BLK promoter. Inhibits KAT6B-dependent transcriptional activation.[7] [8] [9] [10] [PEBB_HUMAN] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBFB enhances DNA binding by RUNX1. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe 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. 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[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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