Targeting protein‐protein interaction networks: Structural genomics of FeS cluster assembly and human cancer biology

Abstract

The NESG is one of four Large‐Scale Centers of the NIGMS Protein Structure Initiative (PSI). A key goal of the PSI is to generate 3D structures for some 5,000 proteins selected using broad biological, genomic, and bioinformatics criteria, together with targets selected from specific biological theme projects, so as to provide significant structural coverage of a large number of protein sequences in nature. The PSI also develops new methods for protein structure analysis, and proactively disseminates these technologies to the broader biological community. Our efforts span three classes of proteins: (i) selected to provide course‐grained coverage of large protein domain families; (ii) nominated in collaborations with the biomedical research community; and (iii) NESG Biomedical Theme of ‘Networks of Proteins Associated with Human Cancer and Developmental Biology’. NESG technology development emphasizes: (i) new technologies for production of proteins, (ii) new methods for protein NMR; (iii) hybrid approaches exploiting synergies of crystallography, SAX, NMR, and computational prediction, and (iv) improved methods for crystallizing proteins. This technology development is driven by our Biomedical Theme focus on human proteins, including protein complexes associated with cancer biology. The many structures, reagents, methods and technologies developed in this project provide starting points for traditional hypothesis‐driven biological research, and provide powerful, broad‐impact infrastructure for biological science and engineering.Supported by Natl. Inst. of General Medical Sciences