Structural and Functional Diversities between Members of the Human HSPB, HSPH, HSPA, and DNAJ Chaperone Families

Abstract

Heat shock proteins (HSPs) were originally identified as stress-responsive proteins required to deal with proteotoxic stresses. Besides being stress-protective and possible targets for delaying progression of protein folding diseases, mutations in chaperones also have been shown to cause disease (chaperonopathies). The mechanism of action of the "classical", stress-inducible HSPs in serving as molecular chaperones preventing the irreversible aggregation of stress-unfolded or disease-related misfolded proteins is beginning to emerge. However, the human genome encodes several members for each of the various HSP families that are not stress-related but contain conserved domains. Here, we have reviewed the existing literature on the various members of the human HSPB (HSP27), HSPH (HSP110), HSPA (HSP70), and DNAJ (HSP40) families. Apart from structural and functional homologies, several diversities between members and families can be found that not only point to differences in client specificity but also seem to serve differential client handling and processing. How substrate specificity and client processing is determined is far from being understood.

Proteostasis in cardiac health and disease

“…HSPs are classified in six sub groups: HSPA (HSP70), HSPB (small HSPs), HSPC (HSP90), HSPD and HSPE (chaperonin families HSP60 and HSP10, respectively), HSPH (HSP110), and DNAJ (HSP40) 29 . Each subgroup comprises several family members and cofactors with distinct and/or overlapping functions, which are localized in various cellular com partments 30,31 . Members can be constitutively expressed or are induced by many different intrinsic or extrin sic stressors 30,[32][33][34] .…”

“…Each subgroup comprises several family members and cofactors with distinct and/or overlapping functions, which are localized in various cellular com partments 30,31 . Members can be constitutively expressed or are induced by many different intrinsic or extrin sic stressors 30,[32][33][34] . HSPs that chaperone de novo pro tein folding and refolding include HSP60, HSP70, and HSP90.…”

“…The human family of small HSPs consists of ten members (HSPB1 to HSPB10) 29 , which share a highly conserved C terminal α crystallin domain 80 . Knowledge about the different functionalities of these ten members of the HSPB fam ily is only beginning to emerge, but data indicate their importance in human pathology as a cause of disease when mutated 30,81 . Several small HSPs, including HSPB1, HSPB5, HSPB6, HSPB7, and HSPB8, are abundantly expressed in the human heart and act to conserve sarco meric and structural proteins 82 .…”

Firefly luciferase mutants as sensors of proteome stress

“…This may be explained by variations in the expression levels of chaperones and other components of the PN within different cell types (Powers et al, 2009;Vos et al, 2008). However, a comprehensive understanding of PN regulation during development and aging is still lacking.…”

The genomic basis of the Williams – Beuren syndrome

“…This is a super family of heat shock proteins (HSPs), known to stimulate the ATPase domain of HSPA chaperones. In the human genome, at least 41 different DNAJ-encoding genes have been identified; the cellular functions are currently unknown for most of its members [158].…”