No abstract

Scattered literature data on biologically active hemoglobin-derived peptides are collected in the form of tables. Respective structure-functional correlations are analyzed and the general conclusion is reached that hemoglobin fragments must have a profound physiological function. Evidence is presented that generation of hemoglobin fragments starts inside the erythrocytes. At that stage alpha- and beta-globin chains of hemoglobin predominantly give rise to relatively long peptides containing ca. 30 amino acid residues. The primary proteolysis is followed by the next degradation step coupled with excretion of newly formed shorter peptides form red blood cells. Both the primary and the secondary proteolysis products are subjected to further stepwise C- and N-terminal chain shortening, giving rise to families of closely related peptides that are actually found in animal tissue extracts. The possible sites of primary proteolysis are compared with the positions of the exposed secondary structure elements within the monomeric alpha- and beta-globins as well as the tetrameric hemoglobin. Two tentative schemes are proposed for hemoglobin degradation, one of which starts at the globin loops exposed on the surface of the tetramer and the other, at monomeric globins where more sites are available for the action of proteases. The concept of a "tissue-specific peptide pool" is formulated, describing a novel system of peptidergic regulation, complementary to the conventional hormonal and neuromodulatory systems. According to that description, hemoglobin is only a single example, although an important one, of a vast number of functional proteins providing their proteolytically derived fragments for maintaining the tissue homeostasis.

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This paper reports a study of the chemistry of valinomycin, enniatins and related membrane-active depsipeptides that increase alkali metal ion permeability of model and biological membranes. The antimicrobial activity of these compounds and their effect on membranes has been correlated with their cation-complexing ability. The complexing reaction has been studied by spectropolarimetric and conductimetric methods. Nuclear magnetic resonance, optical rotatory dispersion, and infrared spectrophotometric studies have revealed the coexistence of conformers of the cyclodepsipeptides in solution and have led to elucidation of the spatial structure of valinomycin, enniatin B and their K(+) complexes. The effect of the conformational properties of the cyclodepsipeptides on their complexation efficiency and selectivity, surface-active properties and behavior towards phospholipid monolayers, bimolecular phospholipid membranes and a number of biological membrane systems has been ascertained. The studies have clearly shown the feasibility of using cyclodepsipeptides with predetermined structural and conformational parameters as chemical tools for membrane studies. it is suggested that the principle of conformation-dependent cation binding through iondipole interactions may possibly lie at the basis of the mode of action of systems governing the natural ion permeability in biological membranes.

No abstract

The structure of the channel-forming polypeptide gramicidin A (GA) incorporated into phosphatidyl-choline (PC) liposomes has been studied as a function of the degree of unsaturation of the acyl chains of PC. The initial conformational state of GA in reconstituted bilayers is determined by the solvent in which the peptide and the lipid are initially co-dissolved, whereas the equilibrium conformational state (after heat incubation) is affected by the lipid structure rather than by the nature of the solvent. The conformational equilibrium of GA has been studied in liposomes prepared from PC having a variable number of double bonds in the fatty acid moiety, by circular dichroism and Fourier transform infrared. Liposomes were prepared from trifluoroethanol or ethanol solutions and incubated at 68 degrees C. GA was shown to retain the conformation of the right-handed pi-->6.3 pi<--6.3 helix in PC with saturated acyl chains and with one double bond, whereas in dilinoleoyl-PC, having two double bond in each chain, the thermodynamically preferred structures are left-handed antiparallel and parallel double pi pi 5.6 helices. Natural soybean PC also favours left-handed pi pi 5.6 helical structures of GA (approximately 75%). This finding is discussed in terms of the role of PC unsaturation in the dynamic properties of the lipid matrix. Differences between observed FTIR spectra of the increases decreases pi pi 5.6 helix in solution (and to a larger extent in the membrane) and the calculated IR spectra can be interpreted as resulting from deviation of the real structure from the theoretically derived ideal helix. The data obtained provide grounds for better understanding of a GA channel functioning in lipids of variable degrees of unsaturation.

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Genomes contain millions of short (<100 codons) open reading frames (sORFs), which are usually dismissed during gene annotation. Nevertheless, peptides encoded by such sORFs can play important biological roles, and their impact on cellular processes has long been underestimated. Here, we analyzed approximately 70,000 transcribed sORFs in the model plant Physcomitrella patens (moss). Several distinct classes of sORFs that differ in terms of their position on transcripts and the level of evolutionary conservation are present in the moss genome. Over 5000 sORFs were conserved in at least one of 10 plant species examined. Mass spectrometry analysis of proteomic and peptidomic data sets suggested that tens of sORFs located on distinct parts of mRNAs and long noncoding RNAs (lncRNAs) are translated, including conserved sORFs. Translational analysis of the sORFs and main ORFs at a single locus suggested the existence of genes that code for multiple proteins and peptides with tissue-specific expression. Functional analysis of four lncRNA-encoded peptides showed that sORFs-encoded peptides are involved in regulation of growth and differentiation in moss. Knocking out lncRNA-encoded peptides resulted in a decrease of moss growth. In contrast, the overexpression of these peptides resulted in a diverse range of phenotypic effects. Our results thus open new avenues for discovering novel, biologically active peptides in the plant kingdom.