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22 Predictions of the Occurrence and Structure of Metal-binding Domains in Gene Regulatory Proteins

Michael H. Schmidt, Jeremy M. Berg


In recent years, metal-binding domains have been found to occur in a wide range of proteins involved in transcriptional regulation. Characterization of these domains by a variety of genetic, chemical, and biophysical methods has revealed that the different classes of these domains adopt a number of unique three-dimensional structures. The common feature shared by these domains is that the bound metal ions act to stabilize conformations of stretches of amino acid sequence on the surfaces of these proteins that are capable of interacting with other macromolecules. The partners of these interactions can include DNA, RNA, or other protein molecules.

The ability to predict the functions and structures of proteins from their amino acid sequences remains a highly desirable but elusive goal. However, for a particular class of proteins involved in nucleic acid binding and gene regulation, some striking successes have been achieved. The major reason for this success is that these proteins bind metal ions such as zinc(II) with all of the residues that coordinate the metal ions occurring within short stretches of amino acid sequence. These metal-binding domains are relatively easily recognized at the primary structural level. Moreover, the ability to assign well-defined roles to certain residues (such as metal binding) has allowed predictions of the three-dimensional structures of all or parts of these metal-binding domains that have proven to be essentially correct. This area of investigation was initiated with the hypothesis that transcription factor IIIA (TFIIIA) from Xenopus oocytes had nine tandem zinc-binding domains that interact...

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