Structure and Function of the Ankyrin Repeats in the SW14/SW16 Transcription Complex of Budding Yeast

摘要

Several ANK repeat-containing proteins have been implicated in breast cancer and other tumor development. Our purpose has been to define the function of the ANK repeats using a combination of genetics and biochemistry. This involved exhaustively mutagenizing the ANK repeats of the yeast Swi6 protein in order to identify the critical residues within each repeat. The effects of these mutations upon DNA binding and transcriptional activity was determined. Partially defective mutants have been identified and used to search for interacting gene products using suppressor analysis. We have concluded that ANK repeats play a structural role. ANK repeats represent one way to stably fold a polypeptide chain, and this structure provides a scaffold upon which different residues can be displayed. It is most likely that the nonconserved residues within the repeats are responsible for the specific protein-protein interactions of each class of ANK repeat proteins. From this we conclude that the right path to understanding the functions of the oncogenic repeat proteins is to focus upon the nonconserved, surface residues within their ANK repeats and search for proteins which interact with them. This work and the available Xray data provide a straight forward path to this goal.