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structure determination of protein-ligand complexes is central in drug development and structural proteomics. To facilitate such high-throughput structure determination we designed an induced replacement strategy. Crystals of a protein complex bound to a photosensitive ligand are exposed to UV light, inducing the departure of the bound ligand, allowing a new ligand to soak in. We exemplify the approach for a class of protein complexes that is especially recalcitrant to high-throughput strategies: the MHC class I proteins. We developed a UV-sensitive, \"conditional\", peptide ligand whose UV-induced cleavage in the crystals leads to the exchange of the low-affinity lytic fragments for full-length peptides introduced in the crystallant solution. This \"in crystallo\" exchange is monitored by the loss of seleno-methionine anomalous diffraction signal of the conditional peptide compared to the signal of labeled MHC beta2m subunit. This method has the potential to facilitate high-throughput crystallography in various protein families.","bibjson":{"author":[{"initials":"PH","lastname":"Celie","name":"Celie PH"},{"initials":"M","lastname":"Toebes","name":"Toebes M"},{"initials":"B","lastname":"Rodenko","name":"Rodenko B"},{"initials":"H","lastname":"Ovaa","name":"Ovaa H"},{"initials":"A","lastname":"Perrakis","name":"Perrakis A"},{"initials":"TN","lastname":"Schumacher","name":"Schumacher TN"}],"identifier":[{"id":"10.1021/ja9037559","type":"doi"},{"id":"19655750","type":"pubmed"}],"issue":["34"],"journal":{"iso_abbreviation":"J. Am. Chem. 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