Cotranslational insertion

Some proteins enter membranes immediately after synthesis. The translocon channel is not required. However, in E. coli an additional protein YidC is needed.603 Homologs of this protein are found in mitochondria (Oxal protein) and in thylakoid membranes of chloroplasts (Alb3 protein).608 These proteins may function in cotranslational insertion. If a protein carries a... 

Leinfelder, W., Zeheleirv, B., Mandrand-Berthelot, M., and Bock, A. (1988). Gene for a novel tRNA Species that accepts L-serinc and cotranslationally inserts seicnocysteine. Nature 331,723-725,... 

APP is expressed in neurons and glia, where it is synthesized and cotranslationally inserted into the endoplasmic reticulum (ER) (90).C)f all the APP mutations identified, most of them take place in the immediate vicinity of the N- and C-terminal of the A/3 fragment or in the middle of its j3-tum area (Fig. 13.1). 

Within the pathogenicity island, there are a number of membrane-inserted proteins, many thought to be involved in export of proteins. The most frequently used protein-secretory pathway is that involving the secretory mechanisms, which relates to cotranslational insertion of a cleavable signal sequence into the translocon. After insertion of this sequence, the rest of the protein is... 

VCP was originally pnrified as a major ATPase associated with endoplasmic reticulum (ER)-derived microsomes, but is also ubiquitous in the cytoplasm and the nucleus [10-12], The BR comprises about half of the total membrane area and one-third of the newly translated proteins in a typical eukaryotic cell [13, 14], Professional secretory cells synthesize 13 million secretory proteins per minute in a crowded environment where BR protein concentrations reach lOOmg/mL [15], After cotranslational insertion into the ER, new proteins undergo folding, assembly, and post-translational modifications, which are scrutinized by a rigorous quality-control mechanism [16], Misfolded proteins which fail to... 

The trace element selenium is present in a number of proteins in the form of cotranslationally inserted selenocysteine (Sec). This insertion occurs when a unique selenocysteinyl-tRNA recognizes an internal UGA codon. Selenocysteine has therefore been called the 21st amino acid and its insertion at a nucleotide triplet that is normally a termination signal represents an expansion of the genetic code. 

Because lysosomal hydrolases are synthesized in the rough ER and cotranslationally modified in the rough ER lumen, a major consideration in I-cell disease enzyme replacement therapy is one involving correct insertion of viable phosphotransferase enzyme in the Golgi. Alternatively, therapy could provide multiple normal enzymes to the lysosomes of abnormal cells. 

A cotranslational mode of selenocysteine insertion necessitates the existence of a tRNA that carries this amino acid. This tRNA was identified during a screening for E. coli mutants blocked in selenoprotein formation. The genes and the function of the gene products found to be involved in selenoprotein synthesis are listed in Table 2. 

The biosynthetic membrane insertion of eukaryotic membrane proteins almost always takes place cotranslationally, whereas many prokaryotic proteins can be posttranslationally inserted, typically with the aid of chaperones. In eukaryotic cells, the proofreading mechanisms in the endoplasmic reticulum prevent misfolded proteins from leaving to the Golgi. Some of these mechanisms include glycosylation of the protein on... 

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