Molecular Chaperones

Definition

Proteins that transiently interact with nascent polypeptide substrates to protect them from misfolding and aggregation. They also have an important role in helping to achieve the native conformation of the newly synthesized protein without forming part of the final folded product. The molecular chaperone HSP90 is responsible for the stability and activity of a range of oncogenic client proteins and is a target for cancer drugs.

Characteristics

Proteins are mediators of a vast array of biological processes, and their activity is dependent on obtaining their correct three-dimensional conformation. It has been widely accepted from in vitro folding experiments that the formation of the native state is a spontaneous process that is dictated by the amino acid sequence of the protein. However, protein folding in vivo is complicated by the crowded cellular environment which naturally favors protein misfolding and aggregation. Under certain conditions, aggregation may lead to the...

Glossary

ATPase

Enzymes that use ATP hydrolysis to yield energy to drive an energetically unfavorable reaction.

Proteasome

A protein degradation complex which can digest a variety of proteins into short polypeptides and amino acids.

Ubiquitination

A posttranslational modification involving the attachment of ubiquitin molecules to specific lysine residues in target proteins. Often this modification acts as a tag for the rapid cellular degradation of the protein by the proteasome.

WD40 repeat

A poorly conserved motif consisting of a repeat sequence containing 40–60 amino acids, which usually contains a Trp-Asp (WD). Several consecutive repeats fold into a domain structure known as a β-propeller in which each section of the structure is a four-stranded β-sheet.