Transporter peptide translocation

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... 

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. 

A further functionally diverse class is made up of the proteins involved in protein biosynthesis and membrane transport. GTPases with functions in protein biosynthesis include the elongation factors, termination factors and peptide translocation factors. These are mostly monomeric proteins with molecular weights of 40 - 50 kDa. 

Lehner PJ, Karttunen JT, Wilkinson GW, Cresswell P (1997) The human cytomegalovirus US6 glycoprotein inhibits transporter associated with antigen processing-dependent peptide translocation. Proc Natl Acad Sci USA 94 6904 6909... 

HCMV affects the cell surface expression of MHC class I molecules and therefore, reduces the antigen presentation for CD8 T lymphocytes (Barnes and Grundy 1992 Beersma et al. 1993 Hengel et al. 1995 Warren et al. 1994 Yamashita et al. 1993). HCMV-infected fibroblasts show a decrease in the peptide transport into the ER (Hengel et al. 1996). A temperature-sensitive mutant of HCMV, ts9, which lacks the genes US1-US15, had lost the capacity to interfere with MHC class I assembly and to inhibit the peptide translocation function of TAP (Hengel et al. 

It has been reported that the plasmid vector is unable to translocate to the nucleus unless complexed in the cytoplasm with nuclear proteins possessing NLS. NLS are short karyophilic peptides on proteins that bind to specific transporter molecules in the cytoplasm, mediating their passage through the pore complexes to the nucleus. Examples of these peptides will be given later in this section. DNA can also be presented to cells in culture as a complex with polycations such as polylysine, or basic proteins such as protamine, total histones or specific histone fractions (110), cationized albumin, and others. These molecules increase the transfection efficiency. In addition histone HI is identified as transfection-enhancing protein in cell culture (111). 

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