Similar folds with different stabilization mechanisms: the cases of Prion and Doppel proteins.

Background: Protein misfolding is the main cause of a group of fatal neurodegenerative diseases in humans and animals. In particular, in Prion-related diseases the normal cellular form of the Prion Protein PrP (PrPC) is converted into the infectious PrPSc through a conformational process during which it acquires a high beta-sheet content. Doppel is a protein that shares a similar native fold, but lacks the scrapie isoform.

The determinants of stability in the human prion protein: insights into folding and misfolding from the analysis of the change in the stabilization energy distribution in different conditions.

The dynamic evolution of the PrP(C) from its NMR-derived conformation to a beta-sheet-rich, aggregation-prone conformation is studied through all-atom, explicit solvent molecular dynamics in different temperature and pH conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach aimed at identifying the key residues for the stabilization and folding of the protein. It is shown that under native conditions the stabilization energy is concentrated in regions of the helices H1 and H3, whereas under misfolding conditions (low pH, high temperature, or mutations in selected sites) it is spread out over helix H2.

Misfolding of the amyloid beta-protein: a molecular dynamics study.

Amyloid beta-proteins spontaneously aggregate and build plaques in the brains of Alzheimer's disease patients. The polypeptide has been the subject of extensive in vitro and computational research. Still, the pathway to aggregational forms and their exact conformations remain largely unclear.

Analysis of the gross anatomical variations found in four cases of trisomy 13.

The variations and defects observed during detailed gross anatomical dissections of four cases of trisomy 13 are described. Emphasis is on the muscular system where previously undocumented variations, absences, and supernumerary elements were observed. A muscle phenotype which includes absence of palmaris longus, palmaris brevis, plantaris, and peroneus tertius, the presence of pectorodorsalis muscles and muscles from the central tendon of the diaphragm to the pericardium near the pulmonary veins, and variations in the extensor indicis, extensor carpi radialis longus and brevis, biceps, and suprahyoid muscles is discussed.