De novo protein folding is delicate and error-prone and requires the guidance of molecular chaperones. Besides cytosolic and organelle-specific chaperones, cells have evolved ribosome-associated chaperones that support early folding events and prevent misfolding and aggregation. This class of chaperones includes the bacterial trigger factor (TF), the archaeal and eukaryotic nascent polypeptide-...

The historical origins and current interpretation of the molecular chaperone concept are presented, with the emphasis on the distinction between folding chaperones and assembly chaperones. Definitions of some basic terms in this field are offered and misconceptions pointed out. Two examples of assembly chaperone are discussed in more detail: the role of numerous histone chaperones in fundamenta...

Complete colorblindness (achromatopsia) is caused by autosomal recessively inherited mutations in the retinal phototransduction pathway, predominantly in the CNGA3and CNGB3-subunit of the cyclic nucleotidegated (CNG) channels in cone photoreceptors. CNGA3, which is mutated in about 25% of the achromatopsia patients, mainly harbors missense mutations which frequently impair the folding and/or tr...

In the last decades NMR spectroscopy has become an invaluable tool both in academic research and in the pharmaceutical industry. This thesis describes applications of NMR spectroscopy in biomedicinal research for structure elucidation of biologically active peptides and peptidomimetics as well as in studies of ligand-protein interactions. The first part of this thesis describes the theory and m...

Protein misfolding is a central feature of most neurodegenerative diseases. Molecular chaperones can modulate the toxicity associated with protein misfolding, but it remains elusive which molecular and co-chaperones interact specific misfolded proteins. TDP-43 inclusion formation are hallmark amyotrophic lateral sclerosis (ALS) other Using yeast mammalian neuronal cells we find that Hsp90 its c...

Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functiona...