Preventing illicit liaisons in Poland

Abstract

This EMBO–FEBS Workshop on the Biology of Molecular Chaperones: Heat Shock Proteins in Molecular Medicine, Misfolding Diseases and Cancer took place from 28 May to 2 June 2005 in Zakopane, Poland, and was organized by U. Hartl and M. Zylicz. ![][1] Although amino‐acid composition and the cellular environment have crucial roles in determining the fold of a nascent polypeptide chain, the polypeptide is often tempted by many ‘illicit liaisons’ before it attains its final, native fold. This is where the chaperones step in to help. Although originally thought simply to prevent these liaisons, it has become increasingly evident that chaperones can also rescue polypeptides that have strayed from the normal folding pathway, sequester misfolded proteins to reduce potentially toxic effects and facilitate the degradation of misfolded proteins by colluding with the ubiquitin–proteasome system (Fig 1). Figure 1. Molecular chaperones are involved in several cellular processes in addition to facilitating folding of the nascent polypeptide chain. Under normal physiological conditions, the polypeptide chain with the help of ribosome‐associated and cytosolic chaperones (C) follows a folding pathway with defined partially folded intermediates (I) that eventually lead to the native folded structure. However, if this folding pathway is in some way perturbed, for example by mutation or cellular stresses such as heat shock, then ‘off‐pathway’ misfolded intermediates may form (I*), which can be prone to form largely unordered aggregates. Such non‐functional aggregates can be dealt with in various ways by the chaperone network, resulting in either restoration of the native structure or sequestration/degradation of the aggregated form. All these aspects of chaperone function were discussed at the meeting. Such quality control is vital for the survival of unicellular and multicellular organisms alike and therefore it is not surprising that there is a high degree of evolutionary conservation of chaperone structure and function. At this … [1]: /embed/graphic-1.gif