Spontaneous fibrillation of the native neuropeptide hormone Somatostatin-14

Somatostatin: A Novel Substrate and a Modulator of Insulin-Degrading Enzyme Activity

“…It has been observed that somatostatin spontaneously selfassembles into a wide molecular range of aggregates and even fibrils. 28 However, since IDE has been reported to hydrolyze only peptides with molecular mass b 6 kDa, 9 it means that IDE should able to hydrolyze only low-molecular-mass species of somatostatin, corresponding to either monomers or small oligomeric forms (up to 6 kDa). Therefore, the high affinity observed for the interaction with IDE (as from the very low K m value, see Table 1) indicates that oligomerization does not seem to impair the recognition by IDE, while the quite slow k cat (see Table 1) might underlie the possibility that the cleavage process is somehow affected by the assembly into small oligomers.…”

“…IDE is able to hydrolyze it at the Phe6-Phe7 bond (see Table 2), confirming that IDE cleaves preferentially peptides showing self-assembly properties, involving basic and/or hydrophobic amino acids. 11,28 Although the factors responsible for its "in vivo" degradation in the brain remain largely unknown, it has been shown that somatostatin is degraded by membrane-associated forms of other Zn-proteases, such as neurolysin and thimet endopeptidase, 26,27 displaying multiple cleavage sites. Here, we show that, indeed, one of these sites is in common with that of IDE (see Fig.…”

Elucidating the Role of Disulfide Bond on Amyloid Formation and Fibril Reversibility of Somatostatin-14

“…Somatostatin-14 (SST- 14) 4 is a small cyclic peptide hormone secreted by hypothalamus, one of the well known functions of which is to inhibit the release of growth hormone (16). Other important functions of somatostatin-14 include inhibition of gastrin and gastric acid secretion, inhibition of insulin and glucagon secretion in pancreas, and regulation of amyloid-␤ peptide, A␤42, in brain (17)(18)(19) Somatostatin-14 has previously been reported to form amyloid fibrils in vitro (4,20). In this study, we first show that somatostatin-14 is stored as amyloid-like aggregates in rat hypothalamus tissues (Fig.…”

“…Both fibrils and monomers (100 M) were separately treated with 20 g/ml proteinase K and incubated at 37°C. At different time points (10,20,30,45,60,80, and 480 min), the digestion profiles of the treated fibril samples relative to monomers were analyzed by mass spectrometry (Autoflex Speed, Bruker MALDI-TOF-TOF mass spectrometer; mass range 1100 -1800; mass tolerance 3 Da). The spectra obtained at different time points were plotted after normalizing peak intensities with respect to the highest intensity peak (base peak) in each spectrum.…”

An ab initio analysis of the structure of l-tryptophan tautomers in microhydrated environments, in water and in hydrophobic solvents

“…Trp is a biochemical precursor taking part in the synthesis of serotonin, niacin, and auxin [2][3][4][5]. In addition, as other aromatic amino acids, Trp plays a major role in enzymatic recognition processes [6,7] as well as in the structural stabilization and self-assembly of some peptides and proteins [8][9][10][11]. Trp also controls important events occurring along electron-transfer pathways in photosynthesis and respiration [12].…”