Translocation target peptides

Loss of translocation competence could result from burial of the signal peptide within the folded precursor, but at least in the case of preMBP, the signal peptide is still accessible as determined by its selective sensitivity to proteolysis and its ability to bind amphiphiles (Dierstein and Wickner, 1985). In the case of the methotrexate-stabilized COX/DHFR fusion, the COX target peptide is clearly accessible since the precursor binds to energized mitochondria (a target peptide-dependent reaction), and the target peptide is susceptible to proteolysis by partially purified matrix processing enzyme (Eilers and Schatz, 1986). 

In order to ensure the cell permeability of the new PROTAC design, an eight amino acid polyarginine tag was included on the carboxy-terminus of the E3 ligase-targeting peptide sequence of the PROTAC. This significant positive charge serves to facilitate translocation of the PROTAC into cells via a mechanism that mimics the HIV Tat protein. ... 

Figure 1 Potential points for the enhancement of liposome-mediated gene transfer. The above diagram illustrates the characteristic lipofection pathway demonstrating the four key stages bold, underlined), complex formation, targeting and internalization, endosomal escape, and nuclear translocation. Indicated alongside (italic) are the peptides that can be used to augment the transfection potential of the liposome. Abbreviation pDNA, plasmid DNA.

The path that leads from full sized protein to epitopes at the cell surface is complex, consisting of the generation of small peptides, translocation of the peptides to the endoplasmic reticulum by a transporter complex, loading of the peptides onto MHC class-I molecules and relocation of the MHC class-I-peptide complex to the cell surface (Rock and Goldberg, 1999). Since many of these steps are known to be prime targets for viral evasion strategies, the next step was to identify at what point the GAr interferes with the presentation of EBNAl. 

Steps in bacterial protein synthesis and targets of (1) chloramphenicol (2) macrolides, clindamycin, and type B streptogramins and (3) tetracyclines. The 70S ribosomal mRNA complex is shown with its 50S and 30S subunits. The peptidyl tRNA at the donor site donates the growing peptide chain to the aminoacyl tRNA at the acceptor site in a reaction catalyzed by peptidyl transferase. The tRNA, discharged of its peptide, is released from the donor site to make way for translocation of the newly formed peptidyl tRNA. The acceptor site is then free to be occupied by the next "charged" aminoacyl tRNA. 

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. 

Roise, D and Maduke, M. (1994) Import of a Mitochondrial Presequence into P. Denitrificans, FEBS Letters, 337, 9-13 Cavalier-Smith, T. (1987) The Simultaneous Symbiotic Origin of Mitochondria, Chloroplasts and Microbodies, Annals of the New York Academy of Science, 503, 55-71 Cavalier-Smith, T. (1992) The Number of Symbiotic Origins of Organelles, BioSystems, 28, 91-106 Hartl, F Ostermann, J., Guiard, B and Neupert, W. (1987) Successive Translocation into and out of the Mitochondrial Matrix Targeting of Proteins to the Inner Membrane Space by a Bipartite Signal Peptide, Cell, 51,1027-1037. 

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