Membrane translocating sequence

Hydrophobic sequences. Including membrane translocating sequences (MTS) (16-18). 

Recently, there has been significant interest in peptidomimetic forms of Tat49 57, not only because of its membrane translocation activity, but as a means of treating HIV infection [1]. Several peptoids, similar in sequence to Tat49 57, have been synthesized with the intention of preventing the HlV-Tat/Tar interaction, and thus preventing HIV replication [24, 25, 30, 31]. However, only recently has this class of peptoids been applied to membrane translocation and dmg delivery applications. 

The amino acid sequences of haptides comprise hydrophobic and cationic residues with a net charge of +4 to +5 per 19 to 21 amino acids. It was proposed that haptides could be attracted to the anionic liposomes as well as the anionic cell membrane and that the hydrophobic properties of the haptide facilitate membrane translocation (106). Haptide uptake was reported to be energy independent, occurring at 4°C. The advantage of this peptide compared to CPP such as TAT and Antp, is that, unlike the virus-derived peptides, the haptides are not recognized as foreign antigens and do not induce cell transformation (106). However, haptides have also been found to accelerate fibrin clot formation and lack cell specificity (106). 

Membrane translocation domains have been identified in toxins and viruses and derived from signal sequences of secreted proteins. When derived from a signal seqnence the translocation domain contains hydrophobic sequences [146-148] while the toxin and viral translocation domains contain mostly basic residues [149,150]. 

A. General description Denileukin dif-titox is a recombinant, DNA-derived, interleukin-2 receptor specific ligand, cytotoxic fusion protein consisting of diphtheria toxin fragments A and B fused to interleukin-2. It is produced by expression of a recombinant fusion protein in Escherichia coli that contains nucleotide sequences for human interleukin-2, and sequences for the enzymatically active fragment A of diphtheria toxin and the membrane-translocating portion of diph-... 

Plant plastocyanins are synthesized in the cytosol as 160-170-ammo acid precursor polypeptides consisting of a 60-70-residue transit peptide followed by a 97 99-amino acid mature protein. The transit peptide imports the precursor plastocyanin molecule across the chloroplast envelope and thylakoid membranes to its final destination in the thylakoid lumen, where it shuttles electrons by accepting them from the membrane bound cytochrome / (cyt /) of the cyt b6/f complex and donating them to the photooxidized reaction center P700-I- of photosystem I. Cyanobacterial plastocyanins use an 30-amino acid leader seqnence for thylakoid membrane translocation. Currently, there are more than 100 plant and cyanobacterial plastocyanin sequences that are available either by direct protein sequencing or deduced from the nucleotide sequences of their genes. 

Protein Import into the chloroplast stroma occurs through inner-membrane and outer-membrane translocation channels that are analogous in function to mitochondrial channels but composed of proteins unrelated in sequence to the corresponding mitochondrial proteins. 

As pointed out by Majerus (1992), none of these three PI-PLC isoforms contains a membrane-spanning sequence. Since the PI substrates for these PI-PLC s are in the membrane bilayers, PI-PLC must bind to membranes before hydrolyzing Pis. The translocation of PI-PLC-71 (induced by its tyrosine phosphorylation) from the cytosol to the cellular membrane (Rhee and Choi, 1992a) may be an example of such a binding. 

Hawiger has developed CPPs derived from the membrane-translocating hydro-phobic sequence of the h-region of the signal peptide sequence of K-FGF [88]. 

Ahn KJ, Paik SR, Chung KC, Kim J. Amino acid sequence motifs and mechanistic features of the membrane translocation of alpha-synuclein. / Neurochem. 2006 97(l) 265-279. 

One notable feature of signal sequences is the absence of any consensus sequence. Their function in protein export is therefore associated with other properties such as hydrophobicity and conformation. Most of the signal sequences of, e.g., /3-lactamase, E. coli alkaline phosphatase, and OmpA, retain their membrane translocation function when they are fused to the N terminus of a variety of heterologous proteins. Despite the heterogeneous appearance, signal sequences present three distinct domains (22) (a) a charged residue within the fiirst five... 

The presence of a signal sequence is not always sufficient to ensure efficient membrane translocation. One feature of the nascent chain that adversely affects secretion, at least in . coli, is the presence of positively charged amino acids immediately downstream of the signal sequence. The downstream sequences form a sharply delimited domain of about 30 residues and, together with the signal sequence, comprise an export initiation domain (26). 

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

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