Protein Engineering, Vol. 12, No. 3, 235-242,
March 1999
© 1999 Oxford University Press
The mechanism of sequence non-specific DNA binding of HMG1/2-box B in HMG1 with DNA
Department of Biological Science and Technology and 1 Frontier Research Center for Computer Science, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
The DNA binding mechanism of box B in HMG1, a member of the sequence non-specific DNA binding HMG1/2-box family of proteins, has been examined by both mutation analyses and molecular modeling techniques. Substitution of the residue 102F, which is characteristically exposed to solvent, with a small hydrophobic amino acid affected its DNA binding activity. However, no additional effect was observed by the further mutation of flanking 101F. Molecular dynamics simulation and modeling studies revealed that 102F intercalates into DNA base-pairs, being supported by the flanking 101F. The mutants with a small hydrophobic residue at position 102 tolerated the substitution for 101F because the side chain at position 102 is too short to intercalate. Thus the intercalation of 102F and the positive effect of the flanking 101F residue are important for the sequence non-specific DNA binding of the HMG1/2-box. The conserved basic residues of 95K, 96R and 109R were also examined for their roles in DNA binding. These residues interacted with DNA mainly by electrostatic interaction and maintained the location of the box on the DNA, which prescribed the intercalation of 102F. The DNA intercalation by HMG1 consists of an ingenious mechanism which brings DNA conformational changes necessary for biological functions.
Keywords: DNA intercalation/HMG1 protein/HMG1/2-box/molecular dynamics/modeling
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