title: Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain.
abstract: Activating transcription factor-2 (ATF-2) is a transcription factor that binds to cAMP response element (CRE). ATF-2 contains two functional domains, an N-terminal transactivation domain and a C-terminal DNA-binding domain. The DNA-binding domain contains the basic leucine zipper (bZip) motif. Here, the three-dimensional structure of the transactivation domain of ATF-2 has been determined by NMR. The transactivation domain consists of two subdomains: the structure of an N-terminal half (N-subdomain) is well determined, while a C-terminal half (C-subdomain) takes a highly flexible and disordered structure. The architecture of the N-subdomain is very similar to that of the well-known zinc finger motif found in DNA-binding domains, consisting of an antiparallel beta-sheet and an alpha-helix. The zinc atom is tetrahedrally coordinated to two cysteine residues and two histidine residues. Amino acids that form the hydrophobic core in all of the DNA-binding zinc fingers are well conserved in the N-subdomain of the transactivation domain, whereas some amino acids that are responsible for binding to the phosphate backbone of DNA in the DNA-binding zinc fingers are substituted with other amino acids. The flexible C-subdomain, which contains two threonine residues that the stress-activated protein kinases phosphorylate, is likely to undergo a conformational change by specific binding to a target protein.
authors: Graduate School of Integrated Science, Yokohama City University, 22-2 Seto Kanazawa-ku, Yokohama, 236-0027, Japan.
authors: A
authors: A
authors: Nagadoi
authors: K
authors: K
authors: Nakazawa
authors: H
authors: H
authors: Uda
authors: K
authors: K
authors: Okuno
authors: T
authors: T
authors: Maekawa
authors: S
authors: S
authors: Ishii
authors: Y
authors: Y
authors: Nishimura
mesh_terms: D051698:Activating Transcription Factor 2; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002942:Circular Dichroism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D016335:Zinc Fingers / Q000235:genetics
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D011994:Recombinant Proteins; D012996:Solutions; D014157:Transcription Factors; D004247:DNA