Protein regulation, protein-protein interactions and structural genomics

The new technical developments and the success of genome sequencing projects have prompted a new approach to scientific investigation and discovery in every field of biochemistry and molecular biology, including structural biology. One of the most prominent recent developments is the birth of structural genomics, a world-wide initiative that aims to provide the three-dimensional structures of all representative proteins. However, structural biology faces an exciting future beyond structural genomics; if we are to understand how the proteome works and use the genomic information for therapeutic purposes, studies of protein-protein interactions and macromolecular complexes, mechanism and regulation of macromolecular function, membrane protein structure, and structure-based therapeutic design must be pursued in parallel. Successful approaches will combine large-scale, high-throughput approaches developed through structural genomics with more traditional hypothesis-driven approaches, supported by integrative bioinformatics tools. The limited funding resources and limited opportunities for involvement in large consortia in a country of the size of Australia require creative strategies in approaching structural biology problems. This article reviews some of the directions pursued by our laboratory, including a 'focused' structural genomics program suited for smaller-scale teams, and studies of protein-protein interactions ( exemplified by the work on nuclear transport proteins and protein kinases) and protein regulation ( exemplified by the work on nuclear transport proteins and phenylalanine hydroxylase).