Caenorhabditis elegans Aging is Associated with a Decline in Proteostasis
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Because of the aforementioned availability of genome-wide RNAi libraries and the ease at which such libraries can be screened for gene knockdown phenotypes in C. elegans, this has usually been the method of choice for the identification of proteostasis network components. One such study involved screening the library for gene inactivations that led to increased or early aggregation of polyQ-YFP in body wall muscle cells [82]. Not surprisingly, this screen revealed that molecular chaperones are required to mitigate polyQ protein misfolding. Interestingly, not all molecular chaperones were identified. Instead, the chaperonin containing TCP-1 (CCT) molecular chaperone complex seems to play a predominant role in this process. Other genes were identified that function at various points along the protein maturation pathway. Specifically, 186 proteins in total were identified, and they included transcription factors, splicing factors, protein elongation factors, and even some proteins involved in protein degradation.
Maple syrup urine disease (branched-chain oxoaciduria)
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The fundamental defect is in the activity of the branched-chain oxoacid dehydrogenase multienzyme complex (Figures 19.1 and 19.2) [1, 6, 7]. The components are E1 (a decarboxylase), E2 (an acyl transferase), and E3 (a flavoprotein lipoamide dehydrogenase (dihydrolipoyl dehydrogenase)). E1 is composed of two proteins in an α2β2 structure. The enzyme complex, which was purified to homogeneity by Pettit and colleagues [7], is analogous to the pyruvate and the 2-ketoglutarate dehydrogenase complexes; in fact, the E3 component of the three complexes is the same protein, and in E3 deficiency (Chapter 50) defective activity of each dehydrogenase enzyme results. Expression studies have shown that the complex does not assemble spontaneously; the E1 α and β proteins require chaperonins for folding and assembly [8].
Bardet−Biedl Syndrome
Dongyou Liu in Handbook of Tumor Syndromes, 2020
BBSome (comprising BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9, and BBS18 subunits) is involved in the trafficking of molecules (e.g., multiple G protein-coupled receptors, melanin-concentrating hormone receptor 1, and somatostatin receptor 3) to the cilium and also in the assembly of intraflagellar transport particles, which mediate bidirectional movement of nonmembrane molecules along the axoneme and between the axoneme and the membrane. The chaperonin-like BBS proteins encoded by the BBS6/MKKS, BBS10, and BBS12 genes share structural homology with the CCT family of group II chaperonins and are indispensable for the formation of BBSome [12]. BBS17 and BBS20 negatively regulate BBSome trafficking. BBS11 encodes an E3 ubiquitin ligase that helps recruit of BBSome. BBS3 mediates the transition between vesicular and intraciliary trafficking, restricts the entry of ciliary vesicle into the cilium, and modulates Wnt signaling. BBS19 encodes a component of the IFT-B complex that links the BBS cargo to IFT machinery [13].
Proteome microarray technology and application: higher, wider, and deeper
Published in Expert Review of Proteomics, 2019
Huan Qi, Fei Wang, Sheng-ce Tao
Differences between the proteins immobilized on microarrays and their counterparts in physiological conditions clearly exist. Traditionally, the proteins used for proteome microarray construction are prepared by an expression system, either cell-based or cell-free. The differences between in post-translational modifications found in expression systems and in physiological conditions might result in different binding patterns. In addition, differences in modification patterns, lack of knowledge of modification sites and functional groups may add extra difficulties to proteins preparation for proteome microarray construction. Protein folding might also be variable among different expression systems because of differences in chaperonins.
Hydrogen deuterium exchange mass spectrometry applied to chaperones and chaperone-assisted protein folding
Published in Expert Review of Proteomics, 2019
Florian Georgescauld, Thomas E. Wales, John R. Engen
Chaperonins constitute an essential class of chaperones formed by two identical rings of about 0.5 MDa each, stacked back to back. Two groups of chaperonins exist: group I chaperonins present in bacteria (GroEL/GroES), mitochondria (Hsp60/Hsp10) and chloroplasts (Cpn60/Cpn10), and group II chaperonins present in eukaryotes (TriC also called CCT) and archaea (thermosome). GroEL/GroES, the most studied chaperonin, is the only essential molecular chaperone in E. coli and interacts with 250 different cytosolic proteins [16]. About 80 of the 250 proteins are ‘strictly dependent’ substrates (or class III substrates) because at 37°C they are unable to acquire their native structure without help from GroEL/GroES and aggregate rapidly. Natural substrates of GroEL/GroES are frequently proteins that include a TIM-barrel domain, with half of the chaperone substrates being of this variety. GroEL consists of a double ring of seven identical subunits forming a central cavity that can hold proteins between 20 and 60 kDa in size. In the presence of ATP and GroES, one substrate protein at a time will be encapsulated for about 10 s in the ‘nano-compartment’ formed by GroEL/GroES, so that folding can occur. Determining how GroEL/GroES actively promotes folding of the encapsulated substrate protein is a key question in the protein folding field. The eukaryotic cognate of GroEL is the chaperonin TRiC, composed of two rings of eight different paralogous subunits (reviewed in [17]). No analogous GroES lid covers the rings in TRiC, but a built-in lid is formed from apical protrusions of each subunit. Substrates of prokaryotic and eukaryotic chaperonins are different, suggesting different functional mechanisms.
Helicobacter hepaticus is required for immune targeting of bacterial heat shock protein 60 and fatal colitis in mice
Published in Gut Microbes, 2021
Verena Friedrich, Ignasi Forné, Dana Matzek, Diana Ring, Bastian Popper, Lara Jochum, Stefanie Spriewald, Tobias Straub, Axel Imhof, Anne Krug, Bärbel Stecher, Thomas Brocker
Chaperonins, a subset of molecular chaperones, control proper protein folding and are present in many bacteria (GroEL) and eukaryotic organelles (heat shock protein (Hsp)60). High similarity and molecular mimicry between the bacterial and human ortholog21 induce antibodies cross-reacting with Hsp60 of both species,22 contributing to IBD and various autoimmune diseases (reviewed in ref. 23). Hsp60 has been suggested as a biomarker and potential pathogenic agent in IBD, as it triggers pro-inflammatory cytokines.23
Related Knowledge Centers
- Bacteria
- Chloroplast
- Protein Folding
- Protein Tertiary Structure
- Organelle
- Heat Shock Protein
- Chaperone
- Adenosine Triphosphate
- Peroxiredoxin
- Endosymbiont