The goal of the MPP is to apply technologies developed by the Protein Structure Initiative (PSI) to investigate the functions of mitochondrial proteins of high biological/biomedical relevance. This is best achieved through collaborations between the MPP and individual investigators that are interested in performing functional follow-up studies in their own laboratories.
To become a collaborator with the MPP, an investigator must first nominate a mitochondrial protein or proteins in an email addressed to firstname.lastname@example.org, with MPP Nomination in the subject line. This nomination must include the name of the gene of interest, the exact DNA sequence of the gene to be analyzed, a brief rationale for why this protein is of particular biological/biomedical interest, and a description of how data from the MPP would motivate/enable follow-up studies. Nominations will be reviewed by MPP staff for feasibility and for any conflicts-of-interest (internally or between existing collaborators). Acceptance of a nomination marks the beginning of a collaboration. It is expected that collaborations will result in publications with joint authorship between the MPP and investigators.
Once a collaboration has been established, the MPP will proceed to clone the nominated gene(s) into vectors suitable for both cell-free and E.coli-based protein production. All proteins produced by these systems will be analyzed for solubility, molecular mass, aggregation/dispersity, and thermal stability. Protein samples that pass these quality control checkpoints will then be passed on for structure determination attempts by X-ray crystallography and/or NMR. Purified protein additionally will be used for MPP functional investigations that may include protein-protein and protein-small molecule interactions, enzymatic analyses, mitochondrial import assays and mitochondrial bioenergetic measurements. More focused follow-up studies may be negotiated on a case-by-case basis. Additionally, purified protein and/clones can be sent to collaborators for work in their own laboratories. Collaborators will be updated on the progress of their proteins as they advance through our experimental pipeline, but will not be able to view progress on proteins nominated by other collaborators.
Each PSI: Biology Center will:
- Ensure that results and data are collected, maintained, and transferred to appropriate databases, including the Protein Data Bank (PDB) and Structural Biology Target Registration Database: Target Track, in a timely fashion.
- Ensure that structure coordinates and structure factors are promptly deposited to the PDB; PSI policy is that coordinates should be deposited within four weeks of completing refinement and must be released immediately upon deposition, unless held temporarily for CASP (Critical Assessment of techniques for protein Structure Prediction) – such as tests of software and methods development.
- Ensure that all appropriate results are provided to the PSI-Structural Biology Knowledge Base.
- Ensure that materials generated by the partnership are shared with qualified scientists through mechanisms including, but not limited to the required deposition of vectors and clones in the PSI-Materials Repository.
- Ensure the timely dissemination of information to the scientific public.
- Ensure that the partnership complies with the intellectual property policies of the partnership institutions, the NIH, and the PSI:Biology Network.