The Mitochondrial Protein Partnership (MPP) was established in July 2010 with the funding 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 are 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 solicits nominations from the scientific community for mitochondrial protein targets of biological/biomedical interest that would be suitable for collaborative study. Once nominations have been approved, collaborative arrangements have been set up, these targets are given high priority, and collaborators are informed of progress made in producing and characterizing the protein in determining structures. Successful collaborations are expected to lead to a joint publication.
A major goal of the MPP will be to screen all human and mouse mitochondrial open reading frames to determine whether they can 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 will be analyzed for solubility, molecular mass, aggregation/dispersity, and thermal stability. Protein samples made in this way will be subject to functional investigations, including protein-protein and protein-small molecule interactions, enzymatic analyses, and mitochondrial import assays.
The Mitochondrial Protein Partnership is supported by NIH/NIGMS grant number U01GM094622.