STRUCTURES AND FUNCTIONS OF CYS3HIS ZINC DOMAINS

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DESCRIPTION: (adapted from applicant's abstract) A variety of classes of proteins involved in the regulation of gene expression have been found to contain short stretches of amino acids that form small structural domains organized around bound zinc ions. Many of these proteins function via interactions with nucleic acids. Two classes that are of current interest are the CCHC-box domain proteins and the CCCH domain proteins. The CCHC-box domain was first identified as a component of proteins from retroviruses where this domain appears to play a key role in the recognition of single stranded DNA. A structural model of these interactions has been developed that will be tested via studies of fragments of a protein that binds to specific single stranded DNA sequences from trypanosomes. The CCCH domain was recognized in the protein Nup475 whose level increases in response to insulin and other growth factors. The functions of CCCH domains are not well established, but recent results suggest that they may cleave specific RNA structures. This proposal reflects a collaborative effort to characterize these two structural motifs using solution state NMR structures as well as functional and binding studies.