Correlated Mutation Analysis of C2H2 Zinc Finger Domains

Abstract

Introduction Zinc finger proteins perform various functions in cellular processes, such as transcription, translation, metabolism and signaling, by binding to nucleic acids or proteins. In a zinc finger domain, a zinc ion forms four coordinate bonds for its stable fold. A C2H2 domain has approximately 25 to 30 amino acid residues, including paired cysteines and histidines as zinc coordinating residues and possessing two short #-strands followed by an #-helix. Most C2H2 zinc finger proteins bind to DNA. Many of the proteins also bind to RNA or proteins. The binding properties depend on the amino acid residues of the zinc finger loop, the arrangement of C2H2 domains in proteins and the higher order structure of proteins [2]. In this research, we analyze C2H2 domains using a method of correlated mutation analysis(CMA). There has been several CMA methods based on substitution matrices [1] or likelihood matrices derived from previously solved structures [3]. We present a CMA method usin