The English (H6R) familial Alzheimer's disease mutation facilitates zinc-induced dimerization of the amyloid-ß metal-binding domain.

Interaction of Zn(2+) with the metal-binding domain of the English (H6R) amyloid-ß mutant results in the formation of peptide dimers. The mutation causes the exclusion of His6 from the zinc chelation pattern observed in the intact domain and triggers the assembly of the dimers via zinc ions coordinated by (11)EVHH(14) fragments.

[Optimization of the methods for small peptide solution structure determination by NMR spectroscopy].

NMR spectroscopy was recognized as a method of protein structure determination in solution. However, determination of the conformation of small peptides, which undergo fast molecular motions, remains a challenge. This is mainly caused by impossibility to collect required quantity of the distance and dihedral angle restraints from NMR spectra. At the same time, short charged peptides play an important role in a number of biological processes, in particular in pathogenesis of neurodegenerative diseases including Alzheimer's disease. Therefore development of a method for structure calculation of small peptides in a water environment using the most realistic force fields seems to be of current importance. Such algorithm has been developed using the Amber-03 force field and software package Gromacs after updating its program code. The algorithm of calculation has been verified on a model peptide for which the solution structure is known, and on the metal binding fragment of rat beta-amyloid for which structure has been determined by alternative methods. The developed algorithm substantially increases quality of structures, in particular Ramachandran plot statistics, and decreases RMSD of coordinates of atoms inside calculated family. The described protocol of calculation can be used for determination of conformation of short peptides, and also for structure optimization of larger proteins containing poorly structured fragments.