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Titolo:
The leukemia-associated AML1 (Runx1)-CBF beta complex functions as a DNA-induced molecular clamp
Autore:
Bravo, J; Li, Z; Speck, NA; Warren, AJ;
Indirizzi:
MRC, Mol Biol Lab, Cambridge CB2 2QH, England MRC Cambridge England CB2 2QH , Mol Biol Lab, Cambridge CB2 2QH, England Dartmouth Coll, Sch Med, Dept Biochem, Hanover, NH 03755 USA Dartmouth Coll Hanover NH USA 03755 , Dept Biochem, Hanover, NH 03755 USA
Titolo Testata:
NATURE STRUCTURAL BIOLOGY
fascicolo: 4, volume: 8, anno: 2001,
pagine: 371 - 378
SICI:
1072-8368(200104)8:4<371:TLA(BC>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORE-BINDING-FACTOR; ACUTE MYELOID-LEUKEMIA; ELECTRON-DENSITY MAPS; RUNT DOMAIN; CLEIDOCRANIAL DYSPLASIA; TRANSCRIPTION FACTOR; AML1/PEBP2-ALPHA-B GENE; MUTATION ANALYSIS; POINT MUTATIONS; PROTEIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Warren, AJ MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England MRC Hills Rd Cambridge England CB2 2QH bridge CB2 2QH, England
Citazione:
J. Bravo et al., "The leukemia-associated AML1 (Runx1)-CBF beta complex functions as a DNA-induced molecular clamp", NAT ST BIOL, 8(4), 2001, pp. 371-378

Abstract

We have determined the structure, at 2.6 Angstrom 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-kappaB/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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:45:46