Longer charged amino acids favor ß-strand formation in hairpin peptides.

Interactions between charged amino acids significantly influence the structure and function of proteins. The encoded charged amino acids Asp, Glu, Arg, and Lys have different number of hydrophobic methylenes linking the backbone to the charged functionality. It remains to be fully understood how does this difference in the number of methylenes affect protein structure stability. Protein secondary structures are the fundamental three-dimensional building blocks of protein structures. ß-Sheet structures are particularly interesting, because these structures have been associated with a number of protein misfolding diseases. Herein, we report the effect of charged amino acid side chain length at two ß-strand positions individually on the stability of a ß-hairpin. The charged amino acids include side chains with a carboxylate, an ammonium, or a guanidinium group. The experimental peptides, fully folded reference peptides, and fully unfolded reference peptides were synthesized by solid phase peptide synthesis and analyzed by 2D NMR methods including TOCSY, DQF-COSY, and ROESY. Sequence specific assignments were performed for all peptides. The chemical shift data were used to derive the fraction folded population and the folding free energy for the experimental peptides. Results showed that the fraction folded population increased with increasing charged amino acid side chain length. These results should be useful for developing functional peptides that adopt the ß-conformation.

New learning and memory related pathways among the hippocampus, the amygdala and the ventromedial region of the striatum in rats.

BACKGROUND: The hippocampus, central amygdaloid nucleus and the ventromedial region (marginal division) of the striatum have been reported to be involved in the mechanism of learning and memory. This study aimed elucidating anatomical and functional connections among these brain areas during learning and memory. RESULTS: In the first part of this study, the c-Fos protein was used to explore functional connections among these structures. Chemical stimulation of either hippocampus or central amygdaloid nucleus results in dense expression of c-Fos protein in nuclei of neurons in the marginal division of the striatum, indicating that the hippocampus and the central amygdaloid nucleus might be functionally connected with the marginal division. In the second part of the study, the cholera toxin subunit B-horseradish peroxidase was injected into the central amygdaloid nucleus to observe anatomical connections among them. The retrogradely transported conjugated horseradish peroxidase was observed in neurons of both the marginal division and dorsal part of the hippocampus following the injection. Hence, neural fibers from both the marginal division and the hippocampus directly projected to the central amygdaloid nucleus. CONCLUSION: The results implicated potential new functional and structural pathways through these brain areas during the process of learning and memory. The pathways ran from ventromedial portion (the marginal division) of the striatum to the central amygdaloid nucleus and then to the hippocampus before going back to the marginal division of the striatum. Two smaller circuits were between the marginal division and the central amygdaloid nucleus, and between the central amygdaloid nucleus and the hippocampus. These connections have added new dimensions of neural networks of learning and memory, and might be involved in the pathogenesis of dementia and Alzheimer disease.