Structural components of SCAN-domain dimerizations.
The SCAN or leucine-rich domain has been characterized as a highly conserved sequence in zinc finger transcription factors that mediates selective dimer formation between SCAN-domain-containing proteins. In order to accommodate various SCAN-domain sequence features, a minimal functional folding unit was defined on the premise of proper structural folding and biochemical binding. The 58-amino acid minimal functional units derived from each of four SCAN-domain protein families were subjected to a three-dimensional position-specific scoring matrix (3D-PSSM) and ungapped threading analysis. The resulting fold prediction represented the SCAN-domain's minimal functional unit as a bundle of three alpha helices folded to a core structure. In addition, the minimal functional folding unit biochemically retained the selective dimerization properties of the native proteins. In order to elucidate the structural components within the SCAN-domain that engage in binding interactions, we attempted to correlate the physicochemical helix properties, as represented by a hydropathy profile, with the experimental dimerization selectivities. The amino-terminal helix revealed the highest diversity measure among the three helices of the minimal functional unit and is therefore likely to offer critical surface-exposed binding residues. Indeed, by interchanging the amino-terminal helix between SCAN-domains without alteration of their structural frames consisting of conserved hydrophobic residues, a modulation of binding preferences was demonstrated. The minimal functional folding unit of SCAN-domains may therefore contain within the amino-terminal alpha helix structural components that determine selective dimerization patterns and combinatorial control of transcription factors.
Nam
Kiyean
K
Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA.
Honer
Christian
C
Schumacher
Christoph
C
D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods; D018076:DNA, Complementary / Q000235:genetics; 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; D000090263:Leucine-Rich Repeat Proteins; D010455:Peptides / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D015534:Trans-Activators
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D000090263:Leucine-Rich Repeat Proteins; D010455:Peptides; D011506:Proteins; D012097:Repressor Proteins; C408468:SCAND1 protein, human; D015534:Trans-Activators; C115745:ZNF202 protein, human; C457300:ZNF24 protein, human