Structure of the SCAN domain from the tumor suppressor protein MZF1.
The SCAN domain mediates interactions between members of a subfamily of zinc-finger transcription factors and is found in more than 60 C2H2 zinc finger genes in the human genome, including the tumor suppressor gene myeloid zinc finger 1 (MZF1). Glutathione-S-transferase pull-down assays showed that the MZF1 SCAN domain self-associates, and a Kd value of 600 nM was measured by intrinsic tryptophan fluorescence polarization. The MZF1 structure determined by NMR spectroscopy revealed a domain-swapped dimer. Each monomer consists of five alpha helices in two subdomains connected by the alpha2-alpha3 loop. Residues from helix 3 of each monomer compose the core of the dimer interface, while the alpha1-alpha2 loop and helix 2 pack against helices 3 and 5 from the opposing monomer. Comprehensive sequence analysis is coupled with the first high-resolution structure of a SCAN dimer to provide an initial view of the recognition elements that govern dimerization for this large family of transcription factors.
Peterson
Francis C
FC
Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road Milwaukee, WI 53226, USA.
Hayes
Paulette L
PL
Waltner
Jeanette K
JK
Heisner
Alicia K
AK
Jensen
Davin R
DR
Sander
Tara L
TL
Volkman
Brian F
BF
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; C408468:SCAND1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors