Weiss M A, Mason K A, Dahl C E, Keutmann H T
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Biochemistry. 1990 Jun 19;29(24):5660-4. doi: 10.1021/bi00476a002.
ZFY, a putative transcription factor encoded by the human Y chromosome, contains a distinctive two-finger repeat: odd-numbered and even-numbered CC/HH metal-binding motifs exhibit systematic alternation in sequence pattern. Such alternation, which is not generally observed in zinc-finger proteins, has also been described in an extensive family of Kruppel-like genes in Xenopus laevis and in the AIDS-associated human DNA-binding protein HIV-EP1. The strict conservation of a two-finger repeat among ZFY-, Kruppel- and HIV-related zinc-finger proteins suggests distinct mechanisms of protein-nucleic acid recognition. To test whether this sequence pattern reflects an underlying alternation in domain structure, we have synthesized and characterized single-finger peptides from the human ZFY gene. Remarkably, systematic differences in metal-dependent folding are observed in the circular dichroism spectra of even- and odd-numbered domains. Our results suggest the existence of distinct CC/HH finger submotifs, which may play different roles in nucleic acid recognition.
ZFY是一种由人类Y染色体编码的假定转录因子，包含一种独特的双指重复序列：奇数和偶数的CC/HH金属结合基序在序列模式上呈现出系统性的交替。这种交替在锌指蛋白中通常未被观察到，在非洲爪蟾的一大类Kruppel样基因家族以及与艾滋病相关的人类DNA结合蛋白HIV-EP1中也有描述。ZFY、Kruppel和HIV相关锌指蛋白中双指重复序列的严格保守性表明了蛋白质与核酸识别的不同机制。为了测试这种序列模式是否反映了结构域结构的潜在交替，我们合成并表征了来自人类ZFY基因的单指肽段。值得注意的是，在偶数和奇数结构域的圆二色光谱中观察到了金属依赖性折叠的系统性差异。我们的结果表明存在不同的CC/HH指亚基序，它们可能在核酸识别中发挥不同的作用。
