Mutagenesis Study on the Zebra Fish SOX9 High-Mobility Group: Comparison of Sequence and Non-Sequence Specific HMG Domains

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• 作者：Nai-Wan Hsiao ; Dharmaraj Samuel ; Yu-Nan Liu ; Li-Chuan Chen ; Tzu-Ying Yang ; Gurunathan Jayaraman ; and Ping-Chiang Lyu
• 刊名：Biochemistry
• 出版年：2003
• 出版时间：September 30, 2003
• 年：2003
• 卷：42
• 期：38
• 页码：11183 - 11193
• 全文大小：559K
• 年卷期：v.42,no.38(September 30, 2003)
• ISSN：1520-4995

文摘

A unique class of proteins, containing high-mobility group (HMG) domain(s), recognizesunusual DNA structures and/or bends specific to AT-rich linear double-stranded DNA. The DNA bindingfeature of these proteins is exhibited in the HMG domain(s). Although the sequence specific and non-sequence specific HMG domains exhibit very high degrees of sequence similarity, the reasons for thedifference between their DNA recognition mechanisms are unclear. A series of zebra fish SOX9 HMGdomain mutants was prepared in an effort to elucidate the importance of various residues on proteinstability and DNA binding. This study is the first of a comprehensive mutagenesis study on a sequencespecific HMG domain. Comparing how various residues influence sequence specific and non-sequencespecific HMG domains helps us to rationalize their mode of action. Positively charged amino acidsconcentrated at the surface of sequence specific HMG domains recognize specific, linear AT-rich DNAsegments. After the negative charges at the surface of the DNA are neutralized, the hydrophobic residuesof the protein may intercalate DNA. Phenylalanine at position 12 plays a crucial role in the sequencespecific HMG domain. The differences in pI values, the instability index, and DNA contact regions betweensequence and non-sequence specific HMG domains are associated with their functional modes.