Mechanisms of Small Heat Shock Proteins.
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ABSTRACT:
SUBMITTER: Janowska MK
PROVIDER: S-EPMC6771367 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Small heat shock proteins (sHsps) are a ubiquitous and ancient family of ATP-independent molecular chaperones. A key characteristic of sHsps is that they exist in ensembles of iso-energetic oligomeric species differing in size. This property arises from a unique mode of assembly involving several parts of the subunits in a flexible manner. Current evidence suggests that smaller oligomers are more active chaperones. Thus, a shift in the equilibrium of the sHsp ensemble allows regulating the chaperone activity. Different mechanisms have been identified that reversibly change the oligomer equilibrium. The promiscuous interaction with non-native proteins generates complexes that can form aggregate-like structures from which native proteins are restored by ATP-dependent chaperones such as Hsp70 family members. In recent years, this basic paradigm has been expanded, and new roles and new cofactors, as well as variations in structure and regulation of sHsps, have emerged.
| S-EPMC6369295 | biostudies-literature
Project description:Small heat-shock proteins (sHSPs) are molecular chaperones that respond to cellular stresses to combat protein aggregation. HSP27 is a critical human sHSP that forms large, dynamic oligomers whose quaternary structures and chaperone activities depend on environmental factors. Upon exposure to cellular stresses, such as heat shock or acidosis, HSP27 oligomers can dissociate into dimers and monomers, which leads to significantly enhanced chaperone activity. The structured core of the protein, the α-crystallin domain (ACD), forms dimers and can prevent the aggregation of substrate proteins to a similar degree as the full-length protein. When the ACD dimer dissociates into monomers, it partially unfolds and exhibits enhanced activity. Here, we used solution-state NMR spectroscopy to characterize the structure and dynamics of the HSP27 ACD monomer. Web show that the monomer is stabilized at low pH and that its backbone chemical shifts, 15N relaxation rates, and 1H-15N residual dipolar couplings suggest structural changes and rapid motions in the region responsible for dimerization. By analyzing the solvent accessible and buried surface areas of sHSP structures in the context of a database of dimers that are known to dissociate into disordered monomers, we predict that ACD dimers from sHSPs across all kingdoms of life may partially unfold upon dissociation. We propose a general model in which conditional disorder-the partial unfolding of ACDs upon monomerization-is a common mechanism for sHSP activity.
| S-EPMC7245567 | biostudies-literature
Project description:Seven genes coding for small heat shock proteins (sHsps) in Bradyrhizobium japonicum have been identified. They are organized in five operons that are coordinately regulated by ROSE, a negatively cis-acting DNA element. The deduced sHsps can be divided into two separate classes: class A, consisting of proteins that show similarity to Escherichia coli IbpA and IbpB, and class B, whose members display significant similarity to other sHsps from prokaryotes and eukaryotes. Two-dimensional gel electrophoresis and Edman sequencing revealed the presence of at least 12 sHsps in B. japonicum, indicating a remarkable abundance of sHsps in this organism. Three additional members of class A and two potentially novel heat shock proteins were identified on the basis of their amino termini. The presence of multiple sHsps was also demonstrated for a variety of Rhizobium and Bradyrhizobium species by immunoblot analysis and two-dimensional gel electrophoresis. An extensive database survey revealed that, in contrast to the rhizobia, other bacteria contain maximally two sHsps whereas many plants have been reported to possess a sHsp superfamily.
| S-EPMC103535 | biostudies-literature
Project description:The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling pathways that regulate macromolecular structure and the biochemical and cellular functions of small HSPs. Cellular processes regulated by small HSPs include chaperoning denatured proteins, maintaining cellular redox state and modifying filamentous actin polymerization. These processes influence smooth muscle proliferation, cell migration, cell survival, muscle contraction and synthesis of signaling proteins. Understanding functions of small heat shock proteins is relevant to mechanisms of disease in which dysfunctional smooth muscle causes symptoms, or is a target of drug therapy. One example is that secreted HSP27 may be a useful marker of inflammation during atherogenesis. Another is that phosphorylated HSP20 which relaxes smooth muscle may prove to be highly relevant to treatment of hypertension, vasospasm, asthma, premature labor and overactive bladder. Because small HSPs also modulate smooth muscle proliferation and cell migration they may prove to be targets for developing effective, novel treatments of clinical problems arising from remodeling of smooth muscle in vascular, respiratory and urogenital systems.
| S-EPMC2581864 | biostudies-literature
Project description:Oligomeric association of human small heat shock proteins HspB1, HspB5, HspB6 and HspB8 was analyzed by means of size-exclusion chromatography, analytical ultracentrifugation and chemical cross-linking. Wild-type HspB1 and Cys mutants of HspB5, HspB6 and HspB8 containing a single Cys residue in position homologous to that of Cys137 of human HspB1 were able to generate heterodimers cross-linked by disulfide bond. Cross-linked heterodimers between HspB1/HspB5, HspB1/HspB6 and HspB5/HspB6 were easily produced upon mixing, whereas formation of any heterodimers with participation of HspB8 was significantly less efficient. The size of heterooligomers formed by HspB1/HspB6 and HspB5/HspB6 was different from the size of the corresponding homooligomers. Disulfide cross-linked homodimers of small heat shock proteins were unable to participate in heterooligomer formation. Thus, monomers can be involved in subunit exchange leading to heterooligomer formation and restriction of flexibility induced by disulfide cross-linking prevents subunit exchange.
| S-EPMC3273557 | biostudies-literature
Project description:The small heat shock proteins (sHsps) are a ubiquitous family of ATP-independent stress proteins found in all domains of life. Drosophila melanogaster Hsp27 (DmHsp27) is the only known nuclear sHsp in insect. Here analyzing sequences from HMMER, we identified 56 additional insect sHsps with conserved arginine-rich nuclear localization signal (NLS) in the N-terminal region. At this time, the exact role of nuclear sHsps remains unknown. DmHsp27 protein-protein interaction analysis from iRefIndex database suggests that this protein, in addition to a putative role of molecular chaperone, is likely involved in other nuclear processes (i.e., chromatin remodeling and transcription). Identification of DmHsp27 interactors should provide key insights on the cellular and molecular functions of this nuclear chaperone.
| S-EPMC7736433 | biostudies-literature
Project description:Small Heat Shock Proteins (sHSPs) evolved early in the history of life; they are present in archaea, bacteria, and eukaryota. sHSPs belong to the superfamily of molecular chaperones: they are components of the cellular protein quality control machinery and are thought to act as the first line of defense against conditions that endanger the cellular proteome. In plants, sHSPs protect cells against abiotic stresses, providing innovative targets for sustainable agricultural production. In humans, sHSPs (also known as HSPBs) are associated with the development of several neurological diseases. Thus, manipulation of sHSP expression may represent an attractive therapeutic strategy for disease treatment. Experimental evidence demonstrates that enhancing the chaperone function of sHSPs protects against age-related protein conformation diseases, which are characterized by protein aggregation. Moreover, sHSPs can promote longevity and healthy aging in vivo. In addition, sHSPs have been implicated in the prognosis of several types of cancer. Here, sHSP upregulation, by enhancing cellular health, could promote cancer development; on the other hand, their downregulation, by sensitizing cells to external stressors and chemotherapeutics, may have beneficial outcomes. The complexity and diversity of sHSP function and properties and the need to identify their specific clients, as well as their implication in human disease, have been discussed by many of the world's experts in the sHSP field during a dedicated workshop in Québec City, Canada, on 26-29 August 2018.
| S-EPMC6439001 | biostudies-literature
Project description:The natural life cycle of many protozoan and helminth parasites involves exposure to several hostile environmental conditions. Under these circumstances, the parasites arouse a cellular stress response that involves the expression of heat shock proteins (HSPs). Small HSPs (sHSPs) constitute one of the main families of HSPs. The sHSPs are very divergent at the sequence level, but their secondary and tertiary structures are conserved and some of its members are related to α-crystallin from vertebrates. They are involved in a variety of cellular processes. As other HSPs, the sHSPs act as molecular chaperones; however, they have shown other activities apparently not related to chaperone action. In this review, the diverse activities of sHSPs in the major genera of protozoan and helminth parasites are described. These include stress response, development, and immune response, among others. In addition, an analysis comparing the sequences of sHSPs from some parasites using a distance analysis is presented. Because many parasites face hostile conditions through its life cycles the study of HSPs, including sHSPs, is fundamental.
| S-EPMC4529861 | biostudies-literature
Project description:Small heat shock proteins (sHsps) are ubiquitous molecular chaperones found in all domains of life, possessing significant roles in protein quality control in cells and assisting the refolding of non-native proteins. They are efficient chaperones against many in vitro protein substrates. Nevertheless, the in vivo native substrates of sHsps are not known. To better understand the functions of sHsps and the mechanisms by which they enhance heat resistance, sHsp-interacting proteins were identified using affinity purification under heat shock conditions. This paper aims at providing some insights into the characteristics of natural substrate proteins of sHsps. It seems that sHsps of prokaryotes, as well as sHsps of some eukaryotes, can bind to a wide range of substrate proteins with a preference for certain functional classes of proteins. Using Drosophila melanogaster mitochondrial Hsp22 as a model system, we observed that this sHsp interacted with the members of ATP synthase machinery. Mechanistically, Hsp22 interacts with the multi-type substrate proteins under heat shock conditions as well as non-heat shock conditions.
| S-EPMC7332586 | biostudies-literature
Project description: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.
| S-EPMC3460807 | biostudies-literature