Peptides energy transduction

Deamer [121] and others have advocated peptide evolution in early protocells capable of energy-transduction. He suggests the first membranes may have been made of monocarboxylic acids and alcohol. However, peptide evolution in protocells lacks any plausible mechanism for heredity of sequence. New sequences (e.g. coding for ligases or proteases) would have to be rediscovered in each lifetime. 

Already in 1965, Ryser and Hancock provided evidence that histones and polyamino acids could greatly enhance albumin uptake by cultured tumor cells (6). More recently, several polybasic peptides (so-called protein transduction domains, PTDs or cell-penetrating peptides, CPPs) have been shown to efficiently mediate uptake of nucleic acids, bioactive peptides, phage particles, and liposomes into a wide variety of mammalian cells. The initially proposed ability of CPPs to penetrate plasma membranes via a temperature-independent, non-endocytotic pathway was later shown to be a fixation artifact, and it is currently widely accepted that CPP-mediated macromolecular delivery follows energy-dependent endocytotic pathways that in most cases depend on the expression of cell-surface heparan sulfate proteoglycans (HSPGs) (7). 

Whether or not transmembrane helix rotation is a crucial event that leads to receptor activation in the case of TNER superfamily, a net effect of ligand binding and receptor activation appears to be the induced closer proximity of the intracellular domains (Eig. 12A), as shovm by fluorescence energy transfer experiments (Ghan et al, 2000). In the structures of TRAF-receptor complexes, the distance between bound receptor peptides is approximately 50 A. This suggests that a distance of separation between the intracellular domains of receptor chains on the order of 50 A may be optimal for TRAP recruitment and signaling transduction. 

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