Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer’s disease

Short neuroprotective peptides, ADNF9 and NAP, are structurally disordered and monomeric in PBS

“…Fig. 1(left panel) shows the spectrum measured at 5 • C, which is consistent with the disordered (irregular) structure [19] as previously reported [13,20,21]. Fig.…”

The structure analysis of Humanin analog, AGA-(C8R)HNG17, by circular dichroism and sedimentation equilibrium: Comparison with the parent molecule

“…Although how the amino acid substitutions would affect the structure of the molecule has not been elucidated, they together enhanced the activity of the parent HNG molecule by 100-fold [9]. Here we show that these substitutions impacted on the structure of the molecule, in particular in water, in which AGA-(C8R)HNG17 has extensive ␤-sheet structure and HNG as well as HN are largely disordered [8,[13][14][15]. Their structure is more similar in PBS.…”

“…The spectral shape characterized by a negative peak around 216 nm, the strong intensity at 216 nm and the positive intensity at 200 nm suggest ␤-sheet structure for the AGA-(C8R)HNG17 [12]. On the contrary, HNG and HN were mostly disordered in water [8,[13][14][15]. Thus, it is possible that this structure difference in water may be responsible for the observed activity difference for the reason described above.…”

d-Ser-containing humanin shows promotion of fibril formation

“…Substitution of Gly for Ser 14 (S14G-HN; HNG) dramatically increases the neuroprotective effect to the same level as that of [DSer 14 ]HN, whereas substitution of Ala for Cys8 (C8A-HN; HNA) abolishes the effect because the molecule can no longer self-dimerize (Hashimoto et al 2001c;Terashita et al 2003). Recently, several groups elucidated the structural features of HN, HNG, and HNA under various conditions (Arakawa et al 2006;Arisaka et al 2008;Benaki et al 2005Benaki et al , 2006Pistolesi et al 2009). However, the structural characteristics of D-Ser-containing HNs, such as [D-Ser 7 ]HN, ] HN,14 ]HN, have not been defined.…”