The dimerization domain of LFB1/HNF1 related transcription factors: a hidden four helix bundle?
LFB1/HNF1 alpha and LFB3/HNF1 beta bind DNA as dimers and form heterodimers together in vivo and in vitro. The dimerization domain has been located in both proteins in the 32 N-terminal residues. In previous papers we have described the conformational stability as determined by CD and the secondary structure by NMR studies of a peptide with the amino acid sequence of the dimerization domain of LFB1/HNF1 alpha. This study presents a more complete characterization of similar synthetic peptides spanning the LFB3/HNF1 beta dimerization domain and the alpha/beta heterodimer. The HNF1 peptides represent an example of structures which cannot be determined by NOE data alone because they are not sufficient to define one unique solution. An approach is presented which combines NMR data, the protein structure database and structural analyses according to known principles of protein structure. On this basis we are able to determine possible solutions and to identify a four helix bundle as the structure most consistent with the experimental evidence.
Pastore
A
A
European Molecular Biology Laboratory, Heidelberg, Germany.
De Francesco
R
R
Castiglione Morelli
M A
MA
Nalis
D
D
Cortese
R
R
D004268:DNA-Binding Proteins / Q000737:chemistry*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D007930:Leucine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D013499:Surface Properties; D014157:Transcription Factors / Q000737:chemistry*
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011522:Protons; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D007930:Leucine