Comparison of the Sequence-Selective DNA Binding by Peptide Dimers with Covalent and Noncovalent Dimerization Domains
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- 作者：Yasunori Aizawa ; Yukio Sugiura ; and Takashi Morii
- 刊名：Biochemistry
- 出版年：1999
- 出版时间：February 2, 1999
- 年：1999
- 卷：38
- 期：5
- 页码：1626 - 1632
- 全文大小：113K
- 年卷期：v.38,no.5(February 2, 1999)
- ISSN：1520-4995
文摘
Sequence-specific DNA binding proteins generally consist of more than two DNA-contactingregions to ensure the selectivity of recognition. The multiple DNA binding modules are connected eitherthrough the covalent linker or through the noncovalent dimerization domain. We have compared the DNAbinding of peptide dimers with covalent and noncovalent dimerization domains to explore the potentialadvantage of each linkage on the sequence-specific DNA binding. Three sets of head-to-tail peptide dimerswere synthesized by using the same basic region peptide to target the same DNA sequence; one dimerwas assembled with a bridged biphenyl derivative as a covalent dimerization domain, and two other dimerswere assembled with the cyclodextrin guest noncovalent dimerization domains. One of the noncovalentdimers was a heterodimer that consisted of cyclodextrin and guest peptides, while the other was ahomodimer that consisted of peptides bearing both cyclodextrin and the guest molecule within the samechain. Both noncovalent dimers formed the specific DNA complexes within narrower ranges of peptideconcentrations and showed higher sequence selectivity than the covalent dimer did. Among the threedimers, the noncovalent homodimer that can form an intramolecular inclusion complex showed the highestsequence selectivity. Because the noncovalent homodimer with the higher stability of the circularintramolecular inclusion complex exhibited the higher sequence selectivity, it was concluded that anequilibrium involving a conformational transition of a monomeric peptide effectively reduced the stabilityof its nonspecific binding complex, hence increasing the efficacy of cooperative dimer formation at thespecific DNA sequence.