Towards Visual Proteomics at High Resolution |
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| Affiliation: | 1. Max-Planck-Institute of Biochemistry, Department for Molecular Structural Biology, Am Klopferspitz 18, 82152 Planegg, Germany;2. Georg-August-University, Institute for Neuropathology, Robert-Koch-Strasse 40, 37075 Göttingen, Germany;3. Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen, Germany |
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| Abstract: | Traditionally, structural biologists approach the complexity of cellular proteomes in a reductionist manner. Proteomes are fractionated, their molecular components purified and studied one-by-one using the experimental methods for structure determination at their disposal. Visual proteomics aims at obtaining a holistic picture of cellular proteomes by studying them in situ, ideally in unperturbed cellular environments. The method that enables doing this at highest resolution is cryo-electron tomography. It allows to visualize cellular landscapes with molecular resolution generating maps or atlases revealing the interaction networks which underlie cellular functions in health and in disease states. Current implementations of cryo ET do not yet realize the full potential of the method in terms of resolution and interpretability. To this end, further improvements in technology and methodology are needed. This review describes the state of the art as well as measures which we expect will help overcoming current limitations. |
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| Keywords: | cryo electron tomography cryo-FIB cryo-CLEM super-resolution light microscopy machine learning Cryo-CLEM" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" Cryo-correlative light and electron microscopy Cryo-EM" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" Cryo-electron microscopy Cryo-ET" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" Cryo-electron tomography Cryo-FM" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" Cryo-fluorescence light microscopy Cryo-FIB" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" Cryo-focused-ion beam Cryo-TEM" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" Transmission electron microscope LPP" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" Laser phase plate SMLM" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" single molecule localization microscopy techniques VPP" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" Volta phase plate |
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