Model of chaperone coordination at the ribosome during multidomain protein synthesis. Short NCs are not recognized by chaperones and can instead sample the ribosome surface (e.g., L29). TF is recruited when the NC elongates beyond ~100 aa,7allowing cotranslational folding in the CTD/PPD cavity and preventing DnaJ (and therefore DnaK) from binding. Burial of hydrophobic surface in an otherwise unfolded intermediate does not release TF, which can also use electrostatic interactions to maintain contact with the NC. Near-natively folded intermediates exclude TF but are recognized by DnaJ, which then recruits DnaK to locally unfolded sites. Longer NCs can simultaneously accommodate both TF and DnaK, resulting in persistent chaperone engagement of even NC segments that are far from the ribosome surface. Termination of synthesis and release from the ribosome allows the NC to escape TF, while domain docking and oligomeric assembly bury sites recognized by DnaJ/K.
