The transporter associated with Ag processing (TAP) translocates antigenic peptides into the endoplasmic reticulum for binding onto MHC class I (MHC I) molecules. Tapasin organizes a peptide-loading complex (PLC) by recruiting MHC I and accessory chaperones to the N-terminal regions (N domains) of the TAP subunits TAP1 and TAP2. To investigate the function of the tapasin-docking sites of TAP in...

molecular chaperones or amyloid-binding compounds?  perspective on their application as possible therapeutic agents in reduction of cytotoxicity of amyloid oligomers

Molecular chaperones assist protein folding by facilitating their "forward" folding and preventing aggregation. However, once aggregates have formed, these chaperones cannot facilitate protein disaggregation. Bacterial ClpB and its eukaryotic homolog Hsp104 are essential proteins of the heat-shock response, which have the remarkable capacity to rescue stress-damaged proteins from an aggregated ...

Heat shock proteins (HSPs) have proven to be effective tools for extending invertebrate lifespan, and in C. elegans daf-2 mutants, longevity resulting from loss of insulin/insulin-like signals is at least partly dependent upon elevated HSP expression. In mice, inhibition of the orthologous growth hormone/insulin-like growth factor I (GH/IGF-I) pathway has similar pro-longevity effects. A recent...

In the past decade, single-molecule fluorescence techniques provided important insights into the structure and dynamics of proteins. In particular, our understanding of the heterogeneous conformational ensembles of unfolded and intrinsically disordered proteins (IDPs) improved substantially by a combination of FRET-based single-molecule techniques with concepts from polymer physics. A complete ...

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...

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...