A general method to map molecular interactions and conformational states in structurally intact cells would find wide application in biochemistry and cell biology. We used a library of imagescalculated on the basis of known structural data-as search templates to detect targets as small as the "head" domain (350 kDa) of the ribosome's small subunit in single-tilt electron cryomicrographs by cellular high resolution template matching (cHRTM). Atomically precise position and orientation estimates reveal the conformation of individual ribosomes and enable the detection of specifically bound ligands down to 24 kDa. We show that highly head-swivelled states are likely to play a role in mRNA translocation in living cells. cHRTM outperforms cryoelectron tomography three-fold in sensitivity and completely avoids the vicissitudes of exogenous labelling. Main:Finding molecular components in intact cells has driven the development of biological imaging techniques, some of which use specific labels, such as fluorescent antibodies, while others rely on a target's intrinsic properties such as its shape (Oliver 1973) and structure (Rickgauer, Grigorieff, and Denk 2017). Labelling is frequently incomplete or nonspecific, can alter the target's interactions with other molecules, provides only moderate precision of localization and
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