Endoplasmic signal peptide

After mRNA splicing, the tropoelastin mRNA is translated at the surface of the rough endoplasmic reticulum (RER) in a variety of cells smooth muscle cells, endothelial and microvascular cells, chondrocytes and fibroblasts. The approximately 70 kDa precursor protein (depending on isoform) is synthesized with an N-terminal 26-amino-acid signal peptide. This nascent polypeptide chain is transported into the lumen of the RER, where the signal peptide is removed cotranslationally [9]. 

A major sorting decision is made early in protein biosynthesis, when specific proteins are synthesized either on free or on membrane-bound polyribosomes. This results in two sorting branches called the cytosolic branch and the rough endoplasmic reticulum (R R) branch (Figure 46-1). This sorting occurs because proteins synthesized on membrane-bound polyribosomes contain a signal peptide that mediates their attachment to the membrane of the ER. Further details on... 

Albumin (69 kDa) is the major protein of human plasma (3.4-4.7 g/dL) and makes up approximately 60% of the total plasma protein. About 40% of albumin is present in the plasma, and the other 60% is present in the extracellular space. The liver produces about 12 g of albumin per day, representing about 25% of total hepatic protein synthesis and half its secreted protein. Albumin is initially synthesized as a preproprotein. Its signal peptide is removed as it passes into the cisternae of the rough endoplasmic reticulum, and a hexapeptide at the resulting amino terminal is subsequently cleaved off farther along the secretory pathway. The synthesis of albumin is depressed in a variety of diseases, particularly those of the liver. The plasma of patients with liver disease often shows a decrease in the ratio of albumin to globulins (decreased albumin-globuhn ratio). The synthesis of albumin decreases rela-... 

Prepro proteins are synthesized with a signal peptide, which directs the protein to the endoplasmic reticulum, where the signal peptide is cleaved thereafter the propeptide is excized and the mature protein or peptide secreted into the circulation. 

The site of synthesis of numerous proteins is remote from their site of function. During transfer from one site to the other, proteins must, therefore, cross cellular membranes [43] [44], Proteins are usually synthesized as precursors containing an amino terminal extension, called the signal (leader) peptide, the sequence of which contains the necessary information to guide the protein to and across a specific membrane. After transmembrane transport (called translocation), the signal peptide is cleaved off by specific signal peptidases, which are found in the rough endoplasmic reticulum, and the... 

Prepro-POMC arises through translation in the rough endoplasmic reticulum (rER). The growing peptide chain is introduced into the ER with the help of a signal peptide. 

They may enter the cytosol and fold quickly into a compact form. This may require only a few seconds, whereas the translation process in the ribosome may take many seconds. The folding will therefore be cotranslational.525 Depending upon the N-terminal signal peptide the protein may later unfold and pass through a membrane pore or translocon into the endoplasmic reticulum (ER), a mitochondrion, chloro-plast, or peroxisome. Wherever it is, it will be crowded together with thousands of other proteins. It will interact with many of these, and evolution will have enabled some of these to become chaperones (discussed in Chapter 10).526... 

All polypeptide hormones are synthesized from mRNA as precursors, which contain signal peptides that direct them into the lumen of the endoplasmic reticulum. In a few cases (e.g., growth hormone and prolactin) no further... 

Processing of insulin. Insulin is synthesized by membrane-bound polysomes in the /3 cells of the pancreas. The primary translation product is preproinsulin, which contains a 24-residue signal peptide preceding the 81-residue proinsulin molecule. The signal peptide is removed by signal peptidase, cutting between Ala (—1) and Phe (+1), as the nascent chain is transported into the lumen of the endoplasmic reticulum. Proinsulin folds and two disulfide bonds crosslink the ends of the molecule as shown. Before secretion, a trypsinlike enzyme cleaves after a pair of basic residues 31, 32 and 59, 60 then a carboxypeptidase B-like enzyme removes these basic residues to generate the mature form of insulin. 

Next, this RNA is translated into a pre-propeptide, which enters the endoplasmic reticulum (Fig. 1—9). This is the precursor of a precursor, sometimes also called the grandparent of the neuropeptide neurotransmitter. This pre-propeptide grandparent neuropeptide has a peptide tail, called a signal peptide, which allows the pre-propeptide to enter the endoplasmic reticulum, where the tail is clipped off by an enzyme called a signal peptidase with formation of the propeptide, or parent of the neuropeptide. The propeptide is the direct precursor of the neuropeptide neurotransmitter itself. 

Secretory proteins have an N-terminal signal peptide which targets the protein to be synthesized on the rough endoplasmic reticulum (RER). During synthesis it is translocated through the RER membrane into the lumen. Vesicles then bud off from the RER and carry the protein to the Golgi complex, where it becomes glycosylated. Other vesicles then carry it to the plasma membrane. Fusion of these transport vesicles with the plasma membrane then releases the protein to the cell exterior. 

The process of protein export involves a small, cytoplasmic ribonucleoprotein particle (the Signal Recognition Particle or SRP) with the signal coding mRNA sequence and/or the signal peptide itself. This interaction stops translation of the protein. Then, the stalled or arrested ribosome moves to the endoplasmic reticulum (ER). A receptor on the ER binds the SRP. 

P, NH2-terminal signal peptide (synthesis and translocation into the endoplasmic reticulum) NH2-terminal D-domains (oligomerization/multimerization -interdimer bonds-, N-glycosylation) Partially repeated or non repeated O-Glycosylated sequences (O-glycosylatlon, sulphatlon)... 

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