Translocation signal peptides

PelZ is a hydrophilic protein of 420 amino acids with a short hydrophobic sequence at its N-terminal end which has Ae characteristics of the signal sequences of exported proteins. The signal peptide may be 24 amino acids long, which would corroborate wiA the usual length encountered in prokaryotes. The molecular cloning of the pelZ gene in an expression vector pT7-6 allowed for the specific 35S-cysteine-methionine raAo-labelling of PelZ in E. coli K38. We could detect, in crude extracts, the presence of a precursor and a mature form of PelZ. After cell fractionation, Ae mature form of PelZ could be localized in Ae periplasm of E. coli. So PelZ appears to be a protein exported by Ae Sec-dependent system of translocation. 

Membrane translocating peptides are promising vehicles for the transfer of macromolecules into the tissues. Recent report of Schwarze et al. [249] demonstrated that a signal peptide from Hl-virus could transfer betagalactosidase protein to virtually all tissues in rat after intravenous and intraperitoneal injections. In the case of proteins, folding phenomena affect their membrane translocation and these features may be different for gene-based drugs. 

The activated MAP kinase exposes a signal peptide that enables it to interact with proteins that promote its translocation into the nucleus. Inside, it catalyzes the phosphorylation of its substrates on Ser-Pro and Thr-Pro motifs. In the case of stimulation by EGF and PDGF, the activation of... 

Most of the arguments described in the sections on bacterial signal peptides and membrane proteins seem to be valid for the eukaryotic systems, as well as the translocation phenomena across the ER membrane (Sakaguchi, 1997). They seem to be also true for the translocation system across the mitochondrial inner membrane protein into the intermembrane space and the system across the thylakoid membrane in chloroplasts. Although the TAT-dependent pathway has not been found in the ER, it exists on the thylakoid membrane (and possibly on the inner membrane of mitochondria). 

The inner envelope membrane proteins have a cleavable N-terminal transit peptide, as well as some hydrophobic domain (s) in their mature portion. There are two possibilities on the role of this hydrophobic domain it may work as an N-terminal signal peptide after the translocation into the stroma and the subsequent cleavage of the transit peptide. Alternatively, it may work as a stop-transfer signal. One more important question is how the distinction is made between the outer membrane proteins, the inner membrane proteins, and the thylakoid membrane proteins. It is still an enigma. 

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... 

Many cells, such as lymphocytes, do however lack efficient internalizing receptor systems. The development of a new and effective internalizing pathway thus appears as a very important goal. Weissleder et al. [83, 96] have tried to develop such a system by attaching a superparamagnetic iron oxide to a membrane translocating signal (MTS) peptide. Several MTSs have been described... 

Figure 16.1 Conceptual multi-component peptide and major cellular barriers in gene transfer. DBS DNA binding signal CTS cytosolic translocation signal NLS nuclear localization signal CRS cell recognition signal, and PEG polyethylene glycol.

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