Schmidli, ClaudioAlbiez, StefanRima, LucaRighetto, RicardoMohammed, InayatullaOliva, PaoloKovacik, LubomirStahlberg, HenningBraun, Thomas2020-02-132020-02-132020-02-132019-07-1010.1073/pnas.1907214116https://infoscience.epfl.ch/handle/20.500.14299/165329High-resolution structural information is essential to understand protein function. Protein-structure determination needs a considerable amount of protein, which can be challenging to produce, often involving harsh and lengthy procedures. In contrast, the several thousand to a few million protein particles required for structure determination by cryogenic electron microscopy (cryo-EM) can be provided by miniaturized systems. Here, we present a microfluidic method for the rapid isolation of a target protein and its direct preparation for cryo-EM. Less than 1 mu L of cell lysate is required as starting material to solve the atomic structure of the untagged, endogenous human 20S proteasome. Our work paves the way for high-throughput structure determination of proteins from minimal amounts of cell lysate and opens more opportunities for the isolation of sensitive, endogenous protein complexes.text::journal::journal article::research article