One size does not fit all: The oligomeric states of αB crystallin

Abstract

Small Heat Shock Proteins (sHSPs) are a diverse family of molecular chaperones that delay protein aggregation through interactions with nonnative and aggregate-prone protein states. This function has been shown to be important to cellular viability and sHSP function/dysfunction is implicated in many diseases, including Alzheimer’s and Alexander disease. Though their gene products are small, many sHSPs assemble into a distribution of large oligomeric states that undergo dynamic subunit exchange. These inherent properties present significant experimental challenges for characterizing sHSP oligomers. Of the ten mammalian sHSPs, the human sHSP 03B1;B crystallin is a paradigm example of sHSP oligomeric properties. Advances in our understanding of sHSP structure, oligomeric distribution, and dynamics have prompted the proposal of several models for the oligomeric states of B. The aim of this review is to highlight characteristics of αB crystallin (αB) that are key to understanding its structure and function. The current state of knowledge, existing models, and outstanding questions that remain to be addressed are presented.

Structure and properties of chimeric small heat shock proteins containing yellow fluorescent protein attached to their C-terminal ends

“…Both the N-terminal and C-terminal ends of sHsp are highly flexible and mobile and have an important role in the formation of sHsp oligomers (Hilton et al 2012;Jehle et al 2011;Delbecq et al 2012;Delbecq and Klevit 2013). The N-terminal domains can be differently oriented in different monomers of the same oligomer; however, at least part of the N-terminal domains is located in the center of oligomers and interact with each other (Jehle et al 2011;Hilton et al 2012).…”

“…The C-terminal ends are also very flexible and are exposed on the surface of oligomers. In addition, they can occupy different positions and interact in at least two different modes with the hydrophobic groove formed by β4 and β8 strands of the same or neighbor dimers inside oligomers (Hilton et al 2012;Baldwin et al 2011;Delbecq et al 2012;Delbecq and Klevit 2013). Attachment of fluorescent protein to the Cterminal end of sHsp tending to form large oligomers (HspB1 and HspB5) might enhance hydrophobic interaction between subunits within the same oligomer or hydrophobic interactions between oligomers, thus leading to the formation of a very large and heterogeneous mixture of different-sized oligomers (Fig.…”

Biophysical chemistry of the ageing eye lens

“…Under normal physiological conditions, sHsps exist bundled into large stable oligomers containing many subunits. Upon encountering physiological stress, these oligomers become unstable and sHsp dimers dissociate into solution (Delbecq and Klevit 2013;Hochberg and Benesch 2014). The active sHsp dimer interacts with aggregating proteins early in their offfolding pathway (Ecroyd and Carver 2009;Fu 2014).…”

“…The α-crystallin domain consists of a β-sandwich structure of 12 β-strands, of which 2 are shared by an adjacent dimerisation partner (Jehle et al 2010). The α-crystallins form dimeric species which together assemble into oligomers composed of this base dimer unit (Delbecq and Klevit 2013). These typically consist of 3 dimer pairs arranged in a ring from which the hexamers then further oligomerise to form a grouping of 40-60 units depending on the conditions (Ecroyd and Carver 2009).…”

The many faces of proteins

“…Another six contributions deal with protein-protein interactions and protein folding [8][9][10][11][12][13]. Two reviews raise the issue of protein behavior in crowded environments such as the living cell [8][9].…”