Transmembrane peptides

Magzoub, M., A. Pramanik, and A. Graslund (2005) Modeling the endosomal escape of cell-penetrating peptides transmembrane pH gradient driven translocation across phospholipid bilayers. Biochemistry 44,14890-14897. 

Connecting peptide Transmembrane Intracytoplasmic 3 untranslated region... 

Fig. 3. (a) Chemical stmcture of a synthetic cycHc peptide composed of an alternating sequence of D- and L-amino acids. The side chains of the amino acids have been chosen such that the peripheral functional groups of the dat rings are hydrophobic and allow insertion into Hpid bilayers, (b) Proposed stmcture of a self-assembled transmembrane pore comprised of hydrogen bonded cycHc peptides. The channel is stabilized by hydrogen bonds between the peptide backbones of the individual molecules. These synthetic pores have been demonstrated to form ion channels in Hpid bilayers (71). 

FIGURE 9.14 Glycophorin A spans the membrane of the hnman erythrocyte via a single ff-helical transmembrane segment. The C-terminns of the peptide, whose sequence is shown here, faces the cytosol of the erythrocyte the N-terminal domain is extracellnlar. Points of attachment of carbohydrate groups are indicated. 

Recently, a variety of natural peptides that form transmembrane channels have been identified and characterized. Melittin (Figure 10.35) is a bee venom toxin peptide of 26 residues. The cecropins are peptides induced in Hyalophora cecropia (Figure 10.36) and other related silkworms when challenged by bacterial infections. These peptides are thought to form m-helical aggregates in mem-... 

The transmembrane potential derived from a concentration gradient is calculable by means of the Nemst equation. If K+ were the only permeable ion then the membrane potential would be given by Eq. 1. With an ion activity (concentration) gradient for K+ of 10 1 from one side to the other of the membrane at 20 °C, the membrane potential that develops on addition of Valinomycin approaches a limiting value of 58 mV87). This is what is calculated from Eq. 1 and indicates that cation over anion selectivity is essentially total. As the conformation of Valinomycin in nonpolar solvents in the absence of cation is similar to that of the cation complex 105), it is quite understandable that anions have no location for interaction. One could with the Valinomycin structure construct a conformation in which a polar core were formed with six peptide N—H moieties directed inward in place of the C—O moieties but... 

Group of transmembrane proteins engaged in the presentation of small peptide fragments to T-cells. Two classes of Major histocompatibility complex (MHC) molecules exist both of which are encoded by a highly polymorphic gene cluster. MHC class I and class II proteins present peptide fragments to CD8+ and CD4+ T-cells, respectively. The human MHC is also known as HLA, the murine MHC as H-2 complex. 

Somatostatin is a regulatory cyclic peptide, which has originally been described as a hypothalamic growth hormone release-inhibiting factor. It is produced throughout the central nervous system (CNS) as well as in secretoty cells of the periphery and mediates its regulatory functions on cellular processes such as neurotransmission, smooth muscle contraction, secretion and cell proliferation via a family of seven transmembrane domain G-protein-coupled receptors termed sstx 5. 

The VACM-1 receptor is a membrane-associated protein with a single putative transmembrane domain that binds selectively AVP (XD — 2 nM), but cannot discriminate between VXR and V2R analogues. It is expressed in endothelial and medullary collecting duct cells and upon stimulation by AVP. It induces a mobilization of cytosolic-free Ca2+, decreases cAMP production and inhibits cellular growth via MAPK phosphorylation and p53 expression. The mechanism of action and physiological functions of this new receptor are not well understood, but it seems to participate in the regulation of AVP induced signal transduction pathways or of a yet unidentified peptide. 

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