The chaperone activity of α-synuclein: Utilizing deletion mutants to map its interaction with target proteins

α-Synuclein is the principal component of the Lewy body deposits that are characteristic of Parkinson's disease. In vivo, and under physiological conditions in vitro, α-synuclein aggregates to form amyloid fibrils, a process that is likely to be associ

The quaternary organization and dynamics of the molecular chaperone HSP26 are thermally regulated

The function of ScHSP26 is thermally controlled: the heat shock that causes the destabilization of target proteins leads to its activation as a molecular chaperone. We investigate the structural and dynamical properties of ScHSP26 oligomers through a combination of multiangle light scattering, fluorescence spectroscopy, NMR spectroscopy, and mass spectrometry. We show that ScHSP26 exists as a heterogeneous oligomeric ensemble at room temperature. At heat-shock temperatures, two shifts in equilibria are observed: toward dissociation and to larger oligomers. We examine the quaternary dynamics of these oligomers by investigating the rate of exchange of subunits between them and find that this not only increases with temperature but proceeds via two separate processes. This is consistent with a conformational change of the oligomers at elevated temperatures which regulates the disassembly rates of this thermally activated protein

Clinical Characteristics of Hypertensive Patients with Obstructive Sleep Apnoea Syndrome Developing Different Types of Left Ventricular Geometry

Objective. The objective of the study was to compare polygraphic parameters and selected laboratory parameters in patients with obstructive sleep apnoea (OSA) who develop various types of left ventricular (LV) geometry. Material and Methods. The research covered 122 patients with obstructive sleep apnoea and coexisting effectively treated systemic hypertension (95 men, 27 women, average age: 54±10.63). Overnight polygraphy, echocardiography, carotid artery ultrasonography, and laboratory measurements were performed. The patients were classified into four groups, depending on LV geometry. Group 1 comprised patients with normal LV geometry, group 2 included those with LV concentric remodelling. Group 3 and group 4 were patients with LV hypertrophy, concentric or eccentric, respectively. Results. The most frequent type of LV geometry in the examined population was eccentric hypertrophy (36%). The highest average values of BMI and T-Ch were observed in the group of patients with concentric remodelling (group 2). The most severe respiratory disorders were found in the group of patients developing LV concentric hypertrophy (group 3); however, these differences were not statistically significant in comparison to other groups. Patients with LV eccentric hypertrophy had significantly decreased LV ejection fraction (p=0.0008). Conclusions. LV eccentric hypertrophy is the most frequent type of LV geometry in OSA patients. Patients with severe sleep-disordered breathing are more likely to develop concentric hypertrophy, while concentric remodelling occurs more frequently among OSA patients with other coexisting conditions, such as obesity or lipid-related disorders

Monitoring the interaction between β2-microglobulin and the molecular chaperone αB-crystallin by NMR and mass spectrometry

The interaction at neutral pH between wild-type and a variant form (R3A) of the amyloid fibril-forming protein β2-microglobulin (β2m) and the molecular chaperone αB-crystallin was investigated by thioflavin T fluorescence, NMR spectroscopy, and mass s