Small heat shock proteins and α-crystallins: Dynamic proteins with flexible functions

Department of Chemistry & Biochemistry, 1007 E. Lowell Street, University of Arizona, Tucson, AZ 85743, USA.
Trends in Biochemical Sciences (Impact Factor: 11.23). 12/2011; 37(3):106-17. DOI: 10.1016/j.tibs.2011.11.005
Source: PubMed


The small heat shock proteins (sHSPs) and the related α-crystallins (αCs) are virtually ubiquitous proteins that are strongly induced by a variety of stresses, but that also function constitutively in multiple cell types in many organisms. Extensive research has demonstrated that a majority of sHSPs and αCs can act as ATP-independent molecular chaperones by binding denaturing proteins and thereby protecting cells from damage due to irreversible protein aggregation. As a result of their diverse evolutionary history, their connection to inherited human diseases, and their novel protein dynamics, sHSPs and αCs are of significant interest to many areas of biology and biochemistry. However, it is increasingly clear that no single model is sufficient to describe the structure, function or mechanism of action of sHSPs and αCs. In this review, we discuss recent data that provide insight into the variety of structures of these proteins, their dynamic behavior, how they recognize substrates, and their many possible cellular roles.

Download full-text


Available from: Elizabeth Vierling, Feb 04, 2014
1 Follower
43 Reads
  • Source
    • "Hsp42 is member of the family of small heat shock proteins (sHsp), which associate with misfolded proteins during aggregation and modulate the aggregate structure in a poorly understood manner. sHsps represent a diverse class of chaperones sharing the -crystallin domain as unifying element [34] [35]). "
    [Show abstract] [Hide abstract]
    ABSTRACT: An evolutionary conserved response of cells to proteotoxic stress is the organized sequestration of misfolded proteins into subcellular deposition sites. In Saccharomyces cerevisiae three major sequestration sites for misfolded proteins exist, IPOD, INQ (former JUNQ) and CytoQ. IPOD is perivacuolar and predominantly sequesters amyloidogenic proteins. INQ and CytoQs are stress-induced deposits for misfolded proteins residing in the nucleus and the cytosol, respectively, and requiring cell compartment-specific aggregases, nuclear Btn2 and cytosolic Hsp42, for formation. The organized aggregation of misfolded proteins is proposed to serve several purposes collectively increasing cellular fitness and survival under proteotoxic stress. These include (i) shielding of cellular processes from interference by toxic protein conformers; (ii) reducing the substrate burden for protein quality control systems upon immediate stress; (iii) orchestrating chaperone and protease functions for efficient repair or degradation of damaged proteins; this involves initial extraction of aggregated molecules via the Hsp70/Hsp104 bi-chaperone system followed by either refolding or proteasomal degradation or removal of entire aggregates by selective autophagy (aggrephagy) involving the adaptor protein Cue5; (iv) enabling asymmetric retention of protein aggregates during cell division, thereby allowing for damage clearance in daughter cells. Regulated protein aggregation thus serves cytoprotective functions vital for the maintenance of cell integrity and survival even under adverse stress conditions and during aging.
    Journal of Molecular Biology 02/2015; 76(7). DOI:10.1016/j.jmb.2015.02.006 · 4.33 Impact Factor
  • Source
    • "The vast majority of sHSPs are localized in the cell cytoplasm, chloroplasts, and mitochondria (Scharf et al., 2001). Many studies have shown that ACD proteins are molecular chaperones, although few studies have demonstrated the function of ACD proteins using knockout mutants (Basha et al., 2012; Horwitz, 1992). Structural "
    [Show abstract] [Hide abstract]
    ABSTRACT: DNA methylation patterns are dynamically controlled by DNA methylation and active DNA demethylation, but the mechanisms of regulation of active DNA demethylation are not well understood. Through forward genetic screens for Arabidopsis mutants showing DNA hypermethylation at specific loci and increased silencing of reporter genes, we identified IDM2 (increased DNA methylation 2) as a regulator of DNA demethylation and gene silencing. IDM2 dysfunction causes DNA hypermethylation and silencing of reporter genes and some endogenous genes. These effects of idm2 mutations are similar to those of mutations in IDM1, a regulator of active DNA demethylation. IDM2 encodes an α-crystallin domain protein in the nucleus. IDM2 and IDM1 interact physically and partially colocalize at discrete subnuclear foci. IDM2 is required for the full activity of H3K18 acetylation but not H3K23 acetylation of IDM1 in planta. Our results suggest that IDM2 functions in active DNA demethylation and in antisilencing by regulating IDM1.
    Molecular Cell 07/2014; 55(3). DOI:10.1016/j.molcel.2014.06.008 · 14.02 Impact Factor
  • Source
    • "A defining feature of small heat-shock proteins is the conserved α-crystallin domain toward the carboxyl terminus (Kriehuber et al. 2010), which existed in all 14 DBM sHSPs, and every DBM sHSP had a characteristic motif " I/V-x-I/V " following the α-crystallin domain. The core α-crystallin domain of sHSPs is a platform for oligomer assembly, and the " I/V-x-I/V " motif is also believed to play a key role in this process (Basha et al. 2012, 2013). Sequence alignment of DBM sHSPs shows that their N-terminal is highly variable. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We identify and characterize 14 small heat-shock protein (sHSP) genes from the diamondback moth (DBM), Plutella xylostella (L.), a destructive pest. Phylogenetic analyses indicate that, except for sHSP18.8 and sHSP19.22, the other 12 DBM sHSPs belong to five known insect sHSP groups. Developmental expression analysis revealed that most sHSPs peaked in the pupal and adult stages. The transcripts of sHSPs display tissue specificity with two exhibiting constitutive expression in four tested tissues. Expression of sHSP18.8 in fourth instar larvae is not induced by the tested abiotic stressors, and unless sHSP21.8 is not sensitive to thermal stress, 12 sHSPs are significantly up-regulated. The messenger RNA (mRNA) levels of all sHSPs are reduced under oxidative stress. Food deprivation leads to significant down-regulation of three sHSPs. The majority of sHSPs show expression variation to various heavy metals, whereas mRNA abundances of sHSP22.1 and sHSP 28.9 are reduced by four heavy metals. The responses of sHSPs to indoxacarb and cantharidin are varied. Beta-cypermethrin and chlorfenapyr exposure results in an increase of 13 sHSP transcripts and a reduction of 12 sHSP transcripts, respectively. These results show that different sHSPs might play distinct roles in the development and regulation of physiological activities, as well as in response to various abiotic stresses of DBM.
    Cell Stress and Chaperones 06/2014; 20(1). DOI:10.1007/s12192-014-0522-7 · 3.16 Impact Factor
Show more