What Happens to a Polypeptide after It is Translated
The folding of many proteins as they spin out of the ribosome is made more efficient by a class of proteins called molecular chaperones which are included among the heat-shock proteins (hsp) because they are synthesized in dramatically increased amounts after exposure to an elevated temperature. The hsps carry out ATP dependent protein folding by preventing temporarily exposed hydrophobic residues from aggregating.
A protein that is associated with the correct arrangement of disulfide bonds is protein disulfide isomerase. Oxidizing environments like the lumen of the ER favor disulfide bonds (as opposed to the cytoplasm which is a highly reducing environment), but this bonding can be wrong. Disulfide isomerase refolds the protein so that the proper disulfide bonds can be formed.
Proteins that fail after translation are quickly removed by the cell in eucaryotes in the proteasome. The proteasome works on proteins that have been specifically marked for destruction by the covalent attachment of copies of a small protein called ubiquitin which is initially activated through its high energy thioester linkage to a cysteine side chain on an ubiquitin activating enzyme (E1). E1 is then transfered to the cysteins on a set of ubiquitin conjugating (E3) proteins. This E2-E3 complex is called ubiquitin ligase and it binds to specific degradation signals in protein substrates. A multiubiquitin chain is formed on the substrate protein which is then recognized by a specific receptor in the proteasome. Regulated control of the destruction of the protein typically either is done through (1) activation of a ubiquitin ligase or (2) activation of a degradation signal. As an example of control, the anaphase promoting complex is a multisubunit ubiquitin ligase that is activated by a cell cycle timed subunit addition at mitosis. The activated APC then causes the degradation of mitotic cyclins.
