Editing Proteolysis (section)

=== Post-translational proteolytic processing ===
Limited proteolysis of a polypeptide during or after [[translation (biology)|translation]] in [[protein biosynthesis|protein synthesis]] often occurs for many proteins. This may involve removal of the [[N-terminal]] [[methionine]], [[signal peptide]], and/or the conversion of an inactive or non-functional protein to an active one. The precursor to the final functional form of protein is termed [[proprotein]], and these proproteins may be first synthesized as preproprotein. For example, [[albumin]] is first synthesized as preproalbumin and contains an uncleaved signal peptide. This forms the proalbumin after the signal peptide is cleaved, and a further processing to remove the N-terminal 6-residue propeptide yields the mature form of the protein.<ref name="creighton">{{cite book |author=Thomas E Creighton |title=Proteins: Structures and Molecular Properties |edition=2nd |pages=[https://archive.org/details/proteinsstructur0000crei/page/78 78–86] |year=1993 |publisher=W H Freeman and Company |isbn=978-0-7167-2317-2 |url=https://archive.org/details/proteinsstructur0000crei/page/78 }}</ref>

==== Removal of N-terminal methionine ====
The initiating methionine (and, in bacteria, [[fMet]]) may be removed during translation of the nascent protein. For ''[[Escherichia coli|E. coli]]'', fMet is efficiently removed if the second residue is small and uncharged, but not if the second residue is bulky and charged.<ref>{{cite journal |author1=P H Hirel |author2=M J Schmitter |author3=P Dessen |author4=G Fayat |author5=S Blanquet |title=Extent of N-terminal methionine excision from Escherichia coli proteins is governed by the side-chain length of the penultimate amino acid |journal=Proc Natl Acad Sci U S A |volume=86|issue=21 |pages=8247–51 |year=1989 |pmid=2682640 |pmc=298257 |doi=10.1073/pnas.86.21.8247|bibcode=1989PNAS...86.8247H |doi-access=free }}</ref> In both [[prokaryotes]] and [[eukaryotes]], the exposed N-terminal residue may determine the half-life of the protein according to the [[N-end rule]].

==== Removal of the signal sequence ====
Proteins that are to be targeted to a particular organelle or for secretion have an N-terminal [[signal peptide]] that directs the protein to its final destination. This signal peptide is removed by proteolysis after their transport through a [[cell membrane|membrane]].

====Cleavage of polyproteins====
Some proteins and most eukaryotic polypeptide hormones are synthesized as a large precursor polypeptide known as a polyprotein that requires proteolytic cleavage into individual smaller polypeptide chains.  The polyprotein [[pro-opiomelanocortin]] (POMC) contains many polypeptide hormones. The cleavage pattern of POMC, however, may vary between different tissues, yielding different sets of polypeptide hormones from the same polyprotein.

Many [[virus (biology)|viruses]] also produce their proteins initially as a single polypeptide chain that were translated from a [[polycistronic]] mRNA. This polypeptide is subsequently cleaved into individual polypeptide chains.<ref name="creighton"/> Common names for the polyprotein include ''gag'' ([[group-specific antigen]]) in [[retrovirus]]es and ''[[ORF1ab]]'' in [[Nidovirales]]. The latter name refers to the fact that a [[slippery sequence]] in the mRNA that codes for the polypeptide causes [[ribosomal frameshift]]ing, leading to two different lengths of peptidic chains (''a'' and ''ab'') at an approximately fixed ratio.

====Cleavage of precursor proteins====
Many proteins and hormones are synthesized in the form of their precursors - [[zymogen]]s, [[proenzyme]]s, and [[prehormone]]s. These proteins are cleaved to form their final active structures. [[Insulin]], for example, is synthesized as [[preproinsulin]], which yields [[proinsulin]] after the signal peptide has been cleaved. The proinsulin is then cleaved at two positions to yield two polypeptide chains linked by two [[disulfide bonds]]. Removal of two C-terminal residues from the B-chain then yields the mature insulin. [[Protein folding]] occurs in the single-chain proinsulin form which facilitates formation of the ultimate inter-peptide disulfide bonds, and the ultimate intra-peptide disulfide bond, found in the native structure of insulin. 
 
Proteases in particular are synthesized in the inactive form so that they may be safely stored in cells, and ready for release in sufficient quantity when required. This is to ensure that the protease is activated only in the correct location or context, as inappropriate activation of these proteases can be very destructive for an organism. Proteolysis of the zymogen yields an active protein; for example, when [[trypsinogen]] is cleaved to form [[trypsin]], a slight rearrangement of the protein structure that completes the active site of the protease occurs, thereby activating the protein.

Proteolysis can, therefore, be a method of regulating biological processes by turning inactive proteins into active ones. A good example is the [[blood clotting cascade]] whereby an initial event triggers a cascade of sequential proteolytic activation of many specific proteases, resulting in blood coagulation. The [[complement system]] of the [[immune response]] also involves a complex sequential proteolytic activation and interaction that result in an attack on invading pathogens.