Hydrophobic signal sequence

The N-terminal hydrophobic signal sequence used to ensure translation on the RER. 

Prepro-a chains containing a hydrophobic signal sequence are synthesized by ribosomes attached to the RER. 

The hydrophobic signal sequence is removed by signal peptidase in the RER to form pro-a chains. 

Protein targetii Secreted or membrane proteins N-terminal hydrophobic signal sequence... 

It had often been assumed that a hydrophobic signal sequence, perhaps folded into a hairpin loop, spontaneously inserts itself into an ER membrane to initiate translocation. However, study of the genetics of protein transport suggests otherwise. Over 50 different genetic loci affect the translocation of proteins in yeast.31/32/33d Products of these secretory genes,... 

Proteins with long C-terminal hydrophobic signal sequences may become attached to phosphatidylinositol-glycan anchors embedded in the plasma membrane (Fig. 8-13). An example is a human alkaline phosphatase in which the a carboxyl of the terminal aspartate residue forms an amide linkage with the ethanolamine part of the anchor. Attachment may occur by a direct attack of the -NH2 group of the ethanolanine on a peptide linkage in a transacylation reaction that releases a 29-residue peptide from the C terminus.118119 (See Chapter 29). 

A hydrophobic signal sequence in the protein being synthesized on a free ribosome directs the ribosome to the endoplasmic reticulum. 

Fig. 4. Nucleotide and deduced amino acid sequence of a cDNA clone encoding human precystatin C. Numbering of the nucleotide sequence starts at the first nucleotide and proceeds in the 5 to 3 direction. Amino acid numbering begins with residue 1 of the mature protein (Gil) and the putative hydrophobic signal sequence thus comprises residues —26 to — 1. The Kozak initiation consensus and the polyadenylation signal are underlined.

A hydrophobic signal sequence at the N-terminus of a secretory protein causes the nascent protein to pass into the lumen of the RER. The signal sequence is cleaved from the N-terminus, and the protein may be glycosylated within the RER. 

The existence of a cis-trans isomerase was first hypothesized and then proved by cloning the cti gene from Pseudomonas strains, followed by purification and characterization of the enzyme. Based on the cis-trans isomerase activity test in different cell compartments, the cytoplasmic membrane was considered as the location of the enzyme, where phospholipids are also present. However, the enzyme was also purified from the periplasmic fraction and this fact was then explained because the isomerase has an N-terminal hydrophobic signal sequence (ca. 

Figure 16-15 shows the hydropathy profiles for three different membrane proteins. The prominent peaks in such plots Identify probable topogenic sequences, as well as their position and approximate length. For example, the hydropathy profile of the human growth hormone receptor reveals the presence of both a hydrophobic signal sequence at the extreme N-termlnus of the protein and an internal hydrophobic stop-transfer sequence (see Figure 16-15a). On the basis...

The mechanism for translocating bacterial proteins across the Inner membrane shares several key features with the translocation of proteins into the ER of eukaryotic cells. First, translocated proteins usually contain an N-termlnal hydrophobic signal sequence, which is cleaved by a signal peptidase. Second, bacterial proteins pass through the Inner membrane In a channel, or translocon, composed of proteins that are structurally similar to the eukaryotic Sec61 complex. Third, bacterial cells express two proteins, Ffh and its receptor (FtsY), that are homologs of the SRP and SRP receptor, respectively. In bacteria, however, these latter proteins appear to function mainly In the insertion of hydrophobic membrane proteins Into the Inner membrane. Indeed, all bacterial proteins that are translocated across the inner membrane do so only after their synthesis In the cytosol is completed but before they are folded Into their final conformation. 

Synthesis begins (Figure 28.38) when an N-terminal hydrophobic signal sequence is synthesized by ribosomes on cytoplasmic mRNA. 

Proteins that are to be exported from the cell, or are to be targeted into mitochondria, are synthesized with a hydrophobic signal sequence of amino acids at the amino terminus to direct them through the membrane. This is removed in the process of post-translational modification. Many other proteins have regions removed from the amino or carboxy terminus during post-translational modification, and the initial (amino-terminal) methionine is removed from most newly synthesized proteins. 

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