Protien Modification

October 2, 2008 by craig

PROTEIN MODIFICATION

TYPES OF MODIFICATION

During protein synthesis and afterwards, proteins can undergo substantial covalent modification. The types(s) and extent of modification will depend on the protein, and often play an important role in the biological function of the protein. In general, protein modifications can be divided into two major classes: reactions on the side chains of the amino acids, and cleavages of the peptide backbone.

The side chains of the amino acids may be modified by Hydroxylation (e.g., proline to hydroxyproline) Methylation (e.g., serine or threonine, at the hydroxyl group)

Acylation (e.g., attachment of a fatty acid, such as stearic, myristic or palmitic acid, to one of several different amino acid side chains) Acetylation (at the side chain amino group of lysine residues in histones) Phosphorylation (of serine, threonine, or tyrosine) Carbohydrate attachment (to serine, threonine, or asparagine; this glycosylation gives rise to “glycoproteins”) One very important type of modification involves the joining of sulfhydryl groups from two cysteine residues into a disulfide bridge, as mentioned earlier in the discussion of the primary level of protein structure. The pairing of the cysteines for bridge formation is done quite specifically, with help from specialized enzyme systems. Disulfide bridge formation frequently occurs during the folding of the protein. Some are even formed on an incompletely synthesized chain during translation. Bridge formation is an important factor in guiding the folding process toward the correct product. The bridges help to stabilize the protein against denaturation and loss of activity. Proteins with mispaired cysteines and incorrectly formed disulfide bridges are often folded in the wrong fashion and are usually biologically inactive.

Backbone cleavages may involve removal of the N-terminal formyl moiety from the methionine, the removal of one or more amino acids at either the N- or Cterminus of the chain, and cuts in the backbone at one or more sites, possibly with the removal of internal peptide sequences.

Besides these modifications, certain proteins can acquire prosthetic groups (e.g., hemes, flavins, iron-sulfur centers, and others). The prosthetic groups may be attached covalently (usually to amino acid side chains) in some cases, noncovalently in others, but in either case they cause a substantial change in the properties of the protein.

PROTEIN TRANSPORT AND MODIFICATION

As the ribosome synthesizes a new peptide chain, the chain usually begins to fold, creating regions of secondary and even incomplete tertiary structure. Enzymes then act on these folded residues to modify them. As noted above, an important modification that occurs at this stage is the formation of disulfide bridges. Another is the cleavage
of the peptide backbone at specific sites, which may be important for the transport of the protein across membranes in the cell. These modifications occur during the process of translation, and so they are described as cotranslational modifications. In eukaryotes, the mature form of a protein may be separated by several membrane barriers from its site of synthesis. For example, proteins secreted from the cell must pass through the membrane of the endoplasmic reticulum (ER) into its lumen, then through channels of the ER (where glycosylation usually occurs) to the Golgi complex. Inside the Golgi complex, there may be further glycosylation; there may also be removal of certain carbohydrate residues or proteolytic cleavage of the protein. Finally the protein passes to secretory vesicles which release the protein outside the plasma membrane of the cell. Proteins destined for other locations inside the cell will receive different types and levels of glycosylation and proteolytic cleavage.

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