1cl3

MOLECULAR INSIGHTS INTO PEBP2/CBF-SMMHC ASSOCIATED ACUTE LEUKEMIA REVEALED FROM THE THREE-DIMENSIONAL STRUCTURE OF PEBP2/CBF BETA

spinqualitylabelsall models 1cl3 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1cl3 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease 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 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 PubMed PEBP2/CBF is a heterodimeric transcription factor essential for genetic regulation of hematopoiesis and osteogenesis. DNA binding by PEBP2/CBF alpha is accomplished by a highly conserved DNA binding domain, the Runt domain (RD), whose structure adopts an S-type immunoglobulin fold when bound to DNA. The supplementary subunit beta enhances DNA binding by the RD in vitro, but its role in the control of gene expression has remained largely unknown in vivo. Chromosome 16 inversion creates a chimeric gene product fusing PEBP2/CBF beta to a portion of the smooth muscle myosin heavy chain (PEBP2/CBF beta-SMMHC) that is causally associated with the onset of acute myeloid leukemia in humans. The three-dimensional structure of PEBP2/CBF beta has been determined in solution and is shown to adopt a fold related to the beta-barrel oligomer binding motif. Direct analysis of a 43.6 kD ternary RD-beta-DNA complex identifies the likely surface of beta in contact with the RD. The structure of PEBP2/CBF beta enables a molecular understanding of the capacity of PEBP2/CBF beta-SMMHC to sequester PEBP2/CBF alpha in the cytoplasm and therefore provides a molecular basis for understanding leukemogenic transformation. Molecular insights into PEBP2/CBF beta-SMMHC associated acute leukemia revealed from the structure of PEBP2/CBF beta.,Goger M, Gupta V, Kim WY, Shigesada K, Ito Y, Werner MH Nat Struct Biol. 1999 Jul;6(7):620-3. PMID:10404215 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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