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A natural eukaryotic chaperonin system [tail-less complex polypeptide 1 (TCP-1) ring complex (TRiC) and its target protein actin] is examined to determine if the active participation of the chaperonin in the folding process is evolutionary-conserved. The results have shown that TRiC has an active role in rearranging the bound actin molecule.

A demonstration that mammalian cells secrete numerous transthyretin (TTR) disease-associated variants with wild-type efficiency in spite of compromised folding energetics, is presented. It is proposed that ER-assisted folding (ERAF) in competition with ER-associated degradation (ERAD) defines the unique secretory aptitude of each tissue.

Results indicate that stability of transthyretin tetramers is dependent on hydrophobic interactions and destabilization is brought about by electrostatic repulsions between two pairs of Lys15 and Lys15' amino acid residues implicating a role for the anion shielding in modulating stability and amyloid fibril formation.

Results show that amyloidogenicity of the soluble human plasma protein, transthyretin, is dependent on tertiary structural changes brought about by acid-mediated dissociation of the homotetramer into monomers. Data further indicate that tetramer to folded monomer transition can not form fibrils, suggesting a need for structural changes within the monomer.

Research has been conducted on the molten globule intermediate of bovine carbonic anhydrase II. The dependence of the stability or unfolding of this intermediate on metal ion cofactor has been investigated.

The use of an anionic oligothipphene derivative (p-FTAA) for detecting prefibrillar protein aggregates during in vitro fibrillation of three different amyloidogenic proteins is analyzed. The results have highlighted the use of p-FTAA as an additional tool for analyzing the process of protein aggregation.

A study related to the single-domain cyclophilin 18 (Cyp18), known to function as a peptidyl-prolyl cis/trans isomerase (PPI) and also function as both a folding catalyst and a chaperone is presented. The chaperone effect of Cyp18 demonstrated for citrate synthase indicated a general chaperone effect of Cyp18 PPI.

Inhibitors based on p-aminobenzoylsulfonamide compounds and 1,3,4-thiadiazolylsulfonamides as well as amino acid activators were employed to study a small-molecule stabilization of the exceptionally destabilized human carbonic anhydrase II (HCA II) mutant H107Y. The findings from the study could be used to design small-molecule folding modulators and possibly autoactivatable molecules for suppression of misfolding of destabilized HCA II mutants which cause Marble brain disease (MBD).

The thermodynamics of destabilizing effects of the H107Y mutation, in human carbonic anhydrase II linked to marble brain disease (MBD) is demonstrated. The results suggest that the mutation is caused by long-range sterical destabilizing effects of the bulky tyrosine residue.

Studies about the specific and directed rearrangement of the [beta]-actin structure observed in the natural [beta]-acting-TRiC system, which is vital for guiding [beta]-actin to the native state is reported.

A study reports the activity, folding, and aggregation behavior of the R200W mutant of the 219-residue soluble extracellular domain of tissue factor [(sub s)TF(sub R200W)] compared to that of the wild-type protein [(sub s)TF(sub wt)]. The study concludes that the lowered activity for FX activation and the propensity of the mutant protein to misfold and aggregate, both would contribute to decreased coagulation activity in TF(sub R200W) carriers.

A negatively charged conjugated polyelectrolyte is developed that displays different characteristic optical changes, detected visually or by adsorption and emission, depending on whether the protein with which it forms a complex is in its native state or amyloid fibril conformation. The formation of amyloid fibrils is reflected as an alteration of the geometry and the electronic structure of the bound polyelectrolyte chains and is detected by absorption and emission.

Research has been conducted on D18G transthyretin. The authors describe the biophysical properties of this transthyretin, and report that it is an unstable monomeric protein.

Human carbonic anhydrase II (HCA II) interacts weakly with GroEL at room temperature. Electron paramagnetic resonance (EPR) spectroscopy was employed to investigate HCA II cysteine mutants spin-labeled at selected positions to further study the interaction. Findings showed that protein-protein interactions can be specifically mapped by site-directed spin-labeling and EPR measurements. HCA II had to be unfolded to approximately the same extent as a GuHCl-induced molten-globule intermediate of the enzyme to interact with GroEL.