2 Assembling a functioning protein
Polypeptides are synthesised by translation of messenger RNA (mRNA) on the ribosome, either in the cytosol or in association with the endoplasmic reticulum (rough ER). The polypeptide starts to adopt elements of secondary structure and to fold even as it is being synthesised, and certain covalent modifications of the polypeptide can also occur while translation is ongoing. Initial folding is rapid (of the order of a few seconds). Some proteins require cofactors, which are non-protein components essential for their function that associate with the polypeptide, via non-covalent interactions, as it folds.
The structure that results from this initial rapid folding is more open and flexible than the final folded polypeptide and is referred to as a molten globule. When synthesis is complete, the structure is precisely adjusted and refined and any further covalent modifications of the protein occur at this stage. Fine-tuning of the polypeptide conformation is a much more lengthy process than the initial folding and in many cases is facilitated by specialised proteins called chaperones. For multisubunit proteins, assembly of the subunits occurs after the individual polypeptides have folded.
The result of all these processes is a mature functional protein (Figure 23).