A Novel Mechanism for Small Heat Shock Proteins to Function as Molecular Chaperones

Zhang, Kaiming; Ezemaduka, Anastasia N.; Wang, Zhao; Hu, Hongli; Shi, Xiaodong; Liu, Chuang; Lu, Xiaoyong; Fu, Xinmiao; Chang, Zengyi; Yin, Chang-Cheng

doi:10.1038/srep08811

Cited by 59 publications

(52 citation statements)

References 50 publications

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“…Upon biotin binding, the avidins gain stability as indicated by their increased Tm values (Table ), which enable and presumably favour the dissociation into dimers. Other studies have indicated an enhanced activity upon dissociation of oligomers , demonstrating a common phenomenon of oligomer dynamics. In certain cases, the congregation of proteins results in additional functions , which have yet to be revealed for afifavidin and hoefavidin.…”

Section: Discussionmentioning

confidence: 79%

Crystal structure of afifavidin reveals common features of molecular assemblage in the bacterial dimeric avidins

2018

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The subfamily of bacterial dimeric avidins is being extended through the discovery of additional members originating from diverse sources. All of these newly discovered dimeric avidin forms exhibit high affinity towards biotin, despite their lack of critical Trp in the classical tetrameric forms. The common feature of forming cylinder‐like multimers (hexamers and octamers) seems to be more than a random occurrence, which generally characterizes their apo forms in the crystalline state and also in some cases in solution. Afifavidin from the Gram‐negative α‐proteobacterium Afifella pfennigii is the fourth member of the subfamily of dimers, which, in the intact apo form, also congregates into octamers both in the solution and in the crystalline state, whereby the C‐terminal extended segments stretch into the biotin‐binding sites of adjacent non‐canonical monomers. The intact apo afifavidin molecule self‐assembles into toroid‐shaped nanostructures that dissociate into the inherent dimers upon binding biotin. On removal of the C‐terminal regions, the short‐form of afifavidin forms dimers both in the solution and in the crystalline states. The high affinity of the dimeric forms of afifavidin towards biotin is maintained, due to the conserved disulfide bridge between L3,4 and L5,6 and the presence of Phe50 in L3,4 that compensate for the lack of the critical Trp in the tetrameric avidins. These cyclic multimeric‐avidin assemblies may be exploited in the future to further diversify biotin‐based nanotechnology or to serve as building blocks in the construction of bio‐inspired materials. Database Structural data are available in the PDB databases under the accession numbers: http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6HDV, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6HDS, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6HDT.

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Section: Discussionmentioning

confidence: 79%

Crystal structure of afifavidin reveals common features of molecular assemblage in the bacterial dimeric avidins

2018

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“…However, relatively little known information is available about CeHSP17 molecular function and properties in C. elegans (Candido, 2002). Recently, we have reported our findings on the ability of CeHSP17 protein to enable growth of Escherichia coli cells at a lethal temperature of 508C (Ezemaduka et al, 2014) and mechanistically show that CeHSP17 protein could exhibit chaperone-like activity in preventing the stress-induced aggregation of model substrate proteins through the formation of super-molecular assemblies (Zhang et al, 2015). Despite these findings, we are still challenged with what CeHSP17 protein does as a molecular chaperone in C. elegans.…”

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confidence: 70%

Chemical Signals of Vector Beetle Facilitate the Prevalence of a Native Fungus and the Invasive Pinewood Nematode

Zhang

Lü

et al. 2017

Journal of Nematology

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Small heat shock proteins (sHSP) are ubiquitously found in all organisms, and with other heat shock proteins (HSP) such as HSP60, HSP70, HSP90, HSP100 made up the molecular chaperone family. They are involved in a wide range of biological processes which include among others cell resistance to biological and environmental stress conditions. In this study, we show by western blotting that CeHSP17, an sHSP of Caenorhabiditis elegans, is significantly induced by high temperatures. Furthermore, in response to metal stress, the CeHSP17 protein expression was significantly induced by cadmium and zinc at high concentration of clearly cytotoxic range in wild-type C. elegans. Altogether, our results show the involvement of CeHSP17 protein in both environmental and biological stresses in C. elegans and establish for the first time the expression pattern of the CeHSP17 protein in response to thermal and metal stress conditions in C. elegans. The responses of CeHSP17 protein expression may serve as potential sensitive biomarker for metal-induced toxicity monitoring and environmental risk assessment.

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“…Heat shock proteins (Hsp) comprise a certain group of highly conserved stress proteins which attracted attention due their overexpression in cancer tissues12. Overexpression of these proteins is related to metastatic potential, resistance to chemotherapy and poor prognosis3.…”

mentioning

confidence: 99%

Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90

Lai

Liu

et al. 2016

Sci Rep

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Two new scalarane sesterterpenoids, 12β-(3′β-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12β-(3′β-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 μg/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase IIα expression. The apoptotic-inducing effect of 3 was supported by the in vivo experiment through suppressing the volume of xenograft tumor growth (47.58%) compared with the control. Compound 1 apoptotic mechanism of action in Molt 4 cells was further elucidated through inducing ROS generation, calcium release and ER stress. Using the molecular docking analysis, 1 exhibited more binding affinity to N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. The expression of Hsp90 client proteins, Akt, p70S6k, NFκB, Raf-1, p-GSK3β, and XIAP, MDM 2 and Rb2, and CDK4 and Cyclin D3, HIF 1 and HSF1 were suppressed by the use of 1. However, the expression of Hsp70, acetylated tubulin, and activated caspase 3 were induced after 1 treatment. Our results suggested that the proapoptotic effect of the isolates is mediated through the inhibition of Hsp90 and topoisomerase activities.

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A Novel Mechanism for Small Heat Shock Proteins to Function as Molecular Chaperones

Cited by 59 publications

References 50 publications

Crystal structure of afifavidin reveals common features of molecular assemblage in the bacterial dimeric avidins

Crystal structure of afifavidin reveals common features of molecular assemblage in the bacterial dimeric avidins

Chemical Signals of Vector Beetle Facilitate the Prevalence of a Native Fungus and the Invasive Pinewood Nematode

Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90

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