Protein secretion translocation site

Plasmodial protein transport (i.e. trafficking) has been proposed to be a multi-step process secretion, translocation across the PVM, movement and specific sorting in the red cell cytoplasm, followed by translocation/ insertion into the target site. Trafficking has recently been the subject of several reviews (Cooke et ah, 2004a Lanzer et ah, 2006 Lingelbach and Przyborski, 2006 Marti et al., 2005 Przyborski et al., 2003 Przyborski and Lanzer, 2005 Tilley et al., 2007 Tonkin et al., 2006 van Ooij and Haidar, 2007). 

Mechanism of action Spironolactone [spye row no LAK tone] is a synthetic aldosterone antagonist that competes with aldosterone for intracellular cytoplasmic receptor sites. The spironolactone-receptor complex is inactive, that is, it prevents translocation of the receptor complex into the nucleus of the target cell, and thus does not bind to DNA. This results in a failure to produce proteins that are normally synthesized in response to aldosterone. These mediator proteins normally stimulate the Na+-K+ exchange sites of the collecting tubule. Thus, a lack of mediator proteins prevents Na+ reabsorption and therefore K+ and H+ secretion. 

Evidence for this model rests primarily on a correlation of lipid biosynthesis and translocation with protein synthesis and secretion. Increased synthesis of one causes increased synthesis of the other (Nesmayanova, 1982 Pag s, 1982). Both are inhibited by dissipation of the membrane potential (Bogdanov et al., 1984). Phosphatidylglycerol is present at the site of protein translocation, and may be involved in binding to the nascent chains and/or the ribosome (Bogdanov et al., 1985b). Bogdanov et al. (1985a) claim that secretion of alkaline phosphatase is accompanied by the appearance in freeze-fracture electron micro-... 

Fig. 9. Maturation pathway of a class II non-lantibiotic bacteriocin presented as a 4-step process. The HPK and RR constitute a protein complex involved in signal transduction of external stimuli (step 1), resulting in transcription and translation of the bacteriocin precursor (step 2). The inactive precursor peptide is targeted to a membrane anchored ATP dependent translocation complex and processing at the double-glycine consensus site occurs intracellularly (step 3) and is followed by secretion (step 4). The role of the accessory protein in this mechanism is not yet understood... 

The phenomenon of thyroid hormone transport encompasses a number of sequential steps beginning with their secretion by the thyroid follicles and ending with their distribution to multiple sites of metabolism and action within virtually all the body s organs. These steps include equilibration with multiple carrier proteins in the plasma, transcapillary passage of both the hormones and the carrier proteins into extravas-cular spaces, entry into cells through their external membranes, and translocation to subcellular compartments and organelles. Some that are the subject of current inquiry or controversy, include the interaction of the hormones with "minor" transport protein in plasma, the kinetics of transcapillary movement, the presence of specific receptors for the carrier proteins and the hormones on endothelial and epithelial cell membranes, and specific transport mechanisms within cell organelles. 

Drugs/toxins Ricin (toxin) from castor oil beans (Ricinus communis) is a ribonuclease that inhibits protein synthesis by cleaving and thus inactivating 28S rRNA. A single molecule of ricin within a cell attacks all the ribosomes and kiUs the ceU Diphtheria toxin an exotoxin secreted by Corynebacterium diphtheriae that inactivates eukaryotic elongation factor 2. A single molecule can kill a ceU Aminoglycosides prevent the formation of the initiation complex Tetracyclines bind to the A site and block the attachment of aminoacyl-tRNA Chloramphenicol inhibits peptidyl transferase (ribozyme) Macrolides and clindamycin bind to the SOS subunit and block translocation... 

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