Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain

Activating transcription factor-2 (ATF-2) is a transcription factor that bi nds to cAMP response element (CRE). ATF-2 contains two functional domains, an N-terminal transactivation domain and a C-terminal DNA-binding domain. T he 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 subdoma ins: the structure of an N-terminal half (N-subdomain) is well determined, while a C-terminal half (C-subdomain) takes a highly flexible and disordere d 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 tetrahed rally coordinated to two cysteine residues and two histidine residues. Amin o acids that form the hydrophobic core in all of the DNA-binding zinc finge rs are well conserved in the N-subdomain of the transactivation domain, whe reas some amino acids that are responsible for binding to the phosphate bac kbone of DNA in the DNA-binding zinc fingers are substituted with other ami no acids. The flexible C-subdomain, which contains two threonine residues t hat the stress-activated protein kinases phosphorylate, is likely to underg o a conformational change by specific binding to a target protein. (C) 1999 Academic Press.