Solution structure of the sequence-specific HMG box of the lymphocyte transcriptional activator Sox-4.
Two groups of HMG box proteins are distinguished. Proteins in the first group contain multiple HMG boxes, are non-sequence-specific, and recognize structural features as found in cruciform DNA and cross-over DNA. The abundant chromosomal protein HMG-1 belongs to this subgroup. Proteins in the second group carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof. A solution structure for the non-sequence-specific C-terminal HMG box of HMG-1 has recently been proposed. Now, we report the solution structure of the sequence-specific HMG-box of the SRY-related protein Sox-4. NMR analysis demonstrated the presence of three alpha-helices (Val10-Gln22, Glu30-Leu41 and Phe50-Tyr65) connected by loop regions (Ser23-Ala49 and Leu42-Pro49). Helices I and II are positioned in an antiparallel mode and form one arm of the HMG box. Helix III is less rigid, makes an average angle of about 90 degrees with helices I and II, and constitutes the other arm of the molecule. As in HMG1B, the overall structure of the Sox-4 HMG box is L-shaped and is maintained by a cluster of conserved, mainly aromatic residues.
Department of Immunology, University Hospital, Utrecht, The Netherlands.
L P
LP
van Houte
V P
VP
Chuprina
M
M
van der Wetering
R
R
Boelens
R
R
Kaptein
H
H
Clevers
D000595:Amino Acid Sequence; D001483:Base Sequence; D002942:Circular Dichroism; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D055751:SOXC Transcription Factors; D017386:Sequence Homology, Amino Acid; D051876:Sex-Determining Region Y Protein; D012996:Solutions; D013379:Substrate Specificity; D015534:Trans-Activators / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors
D017931:DNA Primers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D012996:Solutions; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA