1CL3

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

1CL3 の概要

• エントリーDOI: 10.2210/pdb1cl3/pdb
• 分子名称: POLYOMAVIRUS ENHANCER BINDING PROTEIN 2 (1 entity in total)
• 機能のキーワード: structure from molmol, core-binding factor, gene regulation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (Potential): Q13951
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16228.15

構造登録者

Goger, M.,Gupta, V.,Kim, W.Y.,Shigesada, K.,Ito, Y.,Werner, M.H. (登録日: 1999-05-04, 公開日: 2000-01-01, 最終更新日: 2023-12-27)

主引用文献

Goger, M.,Gupta, V.,Kim, W.Y.,Shigesada, K.,Ito, Y.,Werner, M.H.
Molecular insights into PEBP2/CBF beta-SMMHC associated acute leukemia revealed from the structure of PEBP2/CBF beta
Nat.Struct.Biol., 6:620-623, 1999

PubMed Abstract: 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.

PubMed: 10404215
DOI: 10.1038/10664

実験手法

SOLUTION NMR