Precursor polypeptide

Deshaies, R.J., Koch, B.D., Wemer-Washbume, M., Craig, E.A., Schekman, R. (1988). kA subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332,800-805. 

The term polyproteins is used for two different types of entity. The first refers to precursor polypeptides which are cleaved post-translationally into biologically active proteins or peptides of quite different functions. Examples of these include polyproteins of viruses and some prohormones of vertebrates (reviewed in Kennedy, 2000b). The other type is large proproteins which comprise tandem repetitions of identical or similar polypeptides that are post-translationally cleaved into multiple copies of biochemically similar functional entities. The nematode polyprotein allergens/antigens (NPAs) fall into this class (Fig. 16.1). 

Natriuretic peptides are naturally occurring substances in the body that oppose the activity of the renin-angiotensin system. The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). All three natriuretic peptides are synthesized from cleavage of a larger precursor polypeptide. In the ventricles and brain, the synthesis of BNP predominates ANP is synthesized by cardiac myocytes predominately in the atria and CNP is synthesized in the brain, blood vessels, and kidney. 

Atrial natriuretic peptide is synthesized by cleavage of a larger precursor polypeptide. 

Yaffe MP, Ohta S, Schatz G (1985) A yeast mutant temperature-sensitive for mitochondrial assembly is deficient in a mitochondrial protease activity that cleaves imported precursor polypeptides. EMBO J 4 2069-2074... 

Proteolytic Processing Many proteins are initially synthesized as large, inactive precursor polypeptides that are proteolytically trimmed to form their smaller, active forms. Examples include proinsulin, some viral proteins, and proteases such as chymotrypsinogen and trypsino-gen (see Fig. 6-33). 

Processing pathway of preproopiomelanocortin. This precursor polypeptide is cleaved into a variety of active peptides. With the exception of the signal peptidase cleavage site, the cleavage sites are generally pairs of basic amino acids, although one site contains four. Which active peptides are produced depends on the processing pathway, which varies in different cell types. Thus, in the anterior... 

Atrial natriuretic peptide (ANP) Several active peptides cleaved from precursor polypeptide of 126 residues Smooth muscle relaxation diuretic activity... 

Following messenger formation, the amount and types of proteins can be modulated in additional ways. The initial polypeptide can be processed in various ways so that different polypeptides or proteins are expressed in different tissues. Such a situation exists for processing the precursor polypeptide preproopiomelanocortin (see fig. 24.7). This polypeptide is processed in different ways in the anterior and intermediate lobes of the pituitary gland to give rise to different hormones in these two tissues. 

Note Three distinct families of peptides have been identified the enkephalins, the endorphins, and the dynorphins. Each family is derived from a distinct precursor polypeptide and has a characteristic anatomical distribution. These precursors are now designated as proenkephalin (also proenkephalin A), proopiomelanocortin (POMP), and prodynorphin (also proenkephalin). 

Proteases also are involved in viral maturation. For example, in picomavirus replication the virus RNA is translated into large virus precursor polypeptides. These then are cleaved by a viral protease(s) into the viral proteins (26,27). This opens the possibility that specific inhibitors for the viral processing protease could be used as antiviral agents. 

Adrenocorticotropic hormone derives from the anterior pituitary in response to the leptin-or stress-induced anorexigenic, hypothalamic CRH. Corticotropin (like enkephalins and MSHs) derives from a precursor polypeptide pro-opiomelanocortin. Corticotropin induces the catabolic adrenal cortex corticosteroid cortisol and the mineralocorticoid aldosterone (Chapter 11) and is an important regulator of immune responses including chemotaxis and phagocytosis. Corticotropin acts via GPCRs to activate Gas and increase cAMP in anterior pituitary cells. 

Plant plastocyanins are synthesized in the cytosol as 160-170-ammo acid precursor polypeptides consisting of a 60-70-residue transit peptide followed by a 97 99-amino acid mature protein. The transit peptide imports the precursor plastocyanin molecule across the chloroplast envelope and thylakoid membranes to its final destination in the thylakoid lumen, where it shuttles electrons by accepting them from the membrane bound cytochrome / (cyt /) of the cyt b6/f complex and donating them to the photooxidized reaction center P700-I- of photosystem I. Cyanobacterial plastocyanins use an 30-amino acid leader seqnence for thylakoid membrane translocation. Currently, there are more than 100 plant and cyanobacterial plastocyanin sequences that are available either by direct protein sequencing or deduced from the nucleotide sequences of their genes. 

Julius, D., Blair, L., Brake, A., Sprague, G., and Thorner, J. (1983). Yeast alpha factor is processed from a larger precursor polypeptide the essential role of a membrane-bound dipeptidyl aminopeptidase. Cell 32 839-852. 

Protease inhibitors HfV protease is essential for virus infectivity because protease is needed for viral replication. Protease inhibitors bind reversibly to the active site of HfV protease preventing protease from cleaving the viral precursor polypeptide and blocking viral maturation. Immature viral particles are noninfectious. Amprenavir (APV) Agenerase 50 mg capsule 15 mg/ml solutions Itraconazole, fluconazole, ketoconazole, voriconazole,... 

IL-3 is a glycoprotein, and glycosylation accounts for most of the heterogeneity of this molecule. Depending on the cleavage position of the precursor polypeptide, there are two mature forms of IL-3 a protein with 134 or 140 amino acid residuesd The half-life in the blood is estimated at about 40 minutes. Its structure is a compact globe with four a-helical short chains. 

The substrate, i.e., the virus precursor polypeptide, may be altered so that it cannot be cleaved. This has been accomplished by incorporation of amino acid analogs, incubation at abnormally high tempera-... 

Protease—An enzyme in HIV that cleaves large precursor polypeptides into functional proteins that are necessary to produce a complete... 

Aspartate protease (pol gene encoded) is a viral enzyme that cleaves precursor polypeptides in HIV buds to form the proteins of the mature virus core. The enzyme contains a dipeptide structure not seen in mammalian proteins. Pis bind to this dipeptide, inhibiting the enzyme. 

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