Mitochondrial Protein Partnership (MPP)
The Mitochondrial Protein Partnership (MPP) was established was funded from July 2010 – June 2015 through of a contract from the National Institute of General Medical Sciences (NIH) entitled Partnership for High-Throughput Enabled Biology of the Mitochondrial Proteome. The goals of the MPP were to apply technologies developed by the Protein Structure Initiative (PSI) to problems of interest to the community of biologists and biochemists who investigate the role of mitochondria in human health and disease.
The mitochondrial proteome contains many ORFs, or domains of ORFs, that meet the PSI’s criterion of uniqueness (low sequence similarity to proteins of known structure), many ORFs of major biomedical importance currently unrepresented by three-dimensional structures, and many proteins that lack functional characterization.
The MPP solicited nominations from the scientific community for mitochondrial protein targets of biological/biomedical interest that would be suitable for collaborative study. Once nominations were approved, collaborative arrangements were set up, these targets were given high priority, and collaborators were informed of progress made in producing and characterizing the protein in determining structures. Successful collaborations led to joint publications.
A major goal of the MPP was to screen all human and mouse mitochondrial open reading frames to determine whether they could be used to produce protein samples by an automated in vitro protein production system that utilizes a cell-free wheat germ extract. All proteins produced by this system were analyzed for solubility, molecular mass, aggregation/dispersity, and thermal stability. Protein samples made in this way were subjected to functional investigations, including protein-protein and protein-small molecule interactions, enzymatic analyses, and mitochondrial import assays.