Berg J M
Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218.
Annu Rev Biophys Biophys Chem. 1990;19:405-21. doi: 10.1146/annurev.bb.19.060190.002201.
Many of the hypotheses are clearly correct that are based on the initial observation that TFIIIA has an approximately periodic structure with invariant pairs of cysteines and histidines apparently capable of coordinating metal ions. A startling number of other cDNA clones encode proteins that contain one or more sequences that match the zinc finger consensus, revealing that zinc finger proteins represent perhaps the largest class of DNA binding proteins in eukaryotes and that zinc finger protein-controlled gene expression may be a fundamental aspect of development as well as other processes. A great deal of progress has been made in elucidating the structure of single zinc finger domains. From knowledge of these structures, plausible and testable models can be developed for the complexes between zinc finger proteins and their DNA binding sites. Clearly, one of the most important challenges remaining in this area involves testing and extending these models. Structural data on such protein-nucleic acid complexes derived from NMR or crystallographic studies is tremendously valuable in this regard. Finally, an additional fundamental question is raised by the observation that this family and other important nucleic acid binding proteins contain zinc ions bound in small structural domains. Is zinc binding merely a useful structural strategy for generating domains involved in macromolecular interactions, or are zinc concentration fluctuations used in some manner to regulate gene expression? The biophysical data available to date certainly do not rule out this intriguing possibility.
许多基于最初观察结果的假设显然是正确的，即TFIIIA具有近似周期性的结构，带有明显能够配位金属离子的不变半胱氨酸和组氨酸对。数量惊人的其他cDNA克隆编码的蛋白质含有一个或多个与锌指共有序列匹配的序列，这表明锌指蛋白可能代表真核生物中最大的一类DNA结合蛋白，并且锌指蛋白控制的基因表达可能是发育以及其他过程的一个基本方面。在阐明单个锌指结构域的结构方面已经取得了很大进展。根据这些结构知识，可以为锌指蛋白与其DNA结合位点之间的复合物建立合理且可测试的模型。显然，该领域仍然存在的最重要挑战之一涉及测试和扩展这些模型。在这方面，来自核磁共振（NMR）或晶体学研究的此类蛋白质 - 核酸复合物的结构数据非常有价值。最后，观察到这个家族和其他重要的核酸结合蛋白在小结构域中结合锌离子，这引发了另一个基本问题。锌结合仅仅是一种用于生成参与大分子相互作用的结构域的有用结构策略，还是锌浓度波动以某种方式用于调节基因表达？迄今为止可用的生物物理数据当然不排除这种有趣的可能性。
