SURVEY AND SUMMARY Structural classi®cation of zinc ®ngers

Zinc ®ngers are small protein domains in which zinc plays a structural role contributing to the stability of the domain. Zinc ®ngers are structurally diverse and are present among proteins that perform a broad range of functions in various cellular processes, such as replication and repair, transcription and translation, metabolism and signaling, cell proliferation and apoptosis. Zinc ®ngers typically function as interaction modules and bind to a wide variety of compounds, such as nucleic acids, proteins and small molecules. Here we present a comprehensive classi®cation of zinc ®nger spatial structures. We ®nd that each available zinc ®nger structure can be placed into one of eight fold groups that we de®ne based on the structural properties in the vicinity of the zinc-binding site. Three of these fold groups comprise the majority of zinc ®ngers, namely, C2H2like ®nger, treble clef ®nger and the zinc ribbon. Evolutionary relatedness of proteins within fold groups is not implied, but each group is divided into families of potential homologs. We compare our classi®cation to existing groupings of zinc ®ngers and ®nd that we de®ne more encompassing fold groups, which bring together proteins whose similarities have previously remained unappreciated. We analyze functional properties of different zinc ®ngers and overlay them onto our classi®cation. The classi®cation helps in understanding the relationship between the structure, function and evolutionary history of these domains. The results are available as an online database of zinc ®nger