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Why not high‐throughput eukaryotic protein structures?

During the Phase I and Phase II of the Protein Structure Initiative, the Center for Eukaryotic Structural Genomics focused on developing approaches for high‐throughput structure determination by working with eukaryotics, including humans. Around 9,000 genes were examined, over 1,000 proteins purified to date, and 127 structures determined. Outside requests for studies of over 500 proteins were evaluated. This work suggests expanded efforts with eukaryotic proteins in PSI:Biology will be feasible and can yield many new insights that link structure and function. Based on our experience, effective attack on challenges represented by eukaryotic proteins requires many approaches at all steps in the pipeline from bioinformatics to structure determination. Examples of how different experimental approaches developed by this project are used to prepare and characterize eukaryotic proteins for structure determination will be presented, along with the challenges and opportunities encountered along this path. This work was supported by NIH Protein Structure Initiative Grants P50 GM064598 and NIH U54‐GM074901 (J.L. Markley, PI). The authors thank all members of the CESG team.