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Temperature (Austin, Tex.) 2015Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel sensitive to temperature and chemical stimuli. The importance of temperature and aversive... (Review)
Review
Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel sensitive to temperature and chemical stimuli. The importance of temperature and aversive chemical detection for survival has driven the evolutionary diversity of TRPA1 sensitivity. This diversity can be observed in the various roles of TRPA1 in different species, where it is proposed to act as a temperature-insensitive chemosensor, a heat transducer, a noxious cold transducer, or a detector of low-intensity heat for prey localization. Exploring the variation of TRPA1 functions among species provides evolutionary insight into molecular mechanisms that fine-tune thermal and chemical sensitivity, and offers an opportunity to address basic principles of temperature gating in ion channels. A decade of research has yielded a number of hypotheses describing physiological roles of TRPA1, modulators of its activity, and biophysical principles of gating. This review surveys the diversity of TRPA1 adaptations across evolutionary taxa and explores possible mechanisms of TRPA1 activation.
PubMed: 27227025
DOI: 10.1080/23328940.2014.1000702 -
European Journal of Protistology Jun 2024Chicken coccidiosis causes disastrous losses to the poultry industry all over the world. Eimeria tenella is the most prevalent of these disease-causing species. Our...
Chicken coccidiosis causes disastrous losses to the poultry industry all over the world. Eimeria tenella is the most prevalent of these disease-causing species. Our former RNA-seq indicated that E. tenella ankyrin repeat-containing protein (EtANK) was expressed differently between drug-sensitive (DS) and drug-resistant strains. In this study, we cloned EtANK and analyzed its translational and transcriptional levels using quantitative real-time PCR (qPCR) and western blotting. The data showed that EtANK was significantly upregulated in diclazuril-resistant (DZR) strain and maduramicin-resistant (MRR) strain compared with the drug-sensitive (DS) strain. In addition, the transcription levels in the DZR strains isolated from the field were higher than in the DS strain. The translation levels of EtANK were higher in unsporulated oocysts (UO) than in sporozoites (SZ), sporulated oocysts (SO), or second-generation merozoites (SM), and the protein levels in SM were significantly higher than in UO, SO, and SZ. The results of the indirect immunofluorescence localization showed that the protein was distributed mainly at the anterior region of SZ and on the surface and in the cytoplasm of SM. The fluorescence intensity increased further with its development in vitro. An anti-rEtANK polyclonal antibody inhibited the invasive ability of E. tenella in DF-1 cells. These results showed that EtANK may be related to host cell invasion, required for the parasite's growth in the host, and may be involved in the development of E. tenella resistance to some drugs.
Topics: Eimeria tenella; Protozoan Proteins; Ankyrin Repeat; Animals; Triazines; Chickens; Coccidiostats; Nitriles; Drug Resistance; Coccidiosis; Poultry Diseases; Benzamides; Lactones
PubMed: 38749182
DOI: 10.1016/j.ejop.2024.126089 -
Theranostics 2017Cysteine cathepsins are a group of proteases involved in many physiological and pathological processes. Yet, the selective detection and inhibition of individual...
Cysteine cathepsins are a group of proteases involved in many physiological and pathological processes. Yet, the selective detection and inhibition of individual cathepsins is still challenging. This editorial is discussing the context of a recent work introducing a designed ankyrin repeat protein (DARPin) as novel approach for selective targeting of the protease cathepsin B.
Topics: Cathepsin B; Cathepsins; Cysteine; Humans; Neoplasms
PubMed: 28824729
DOI: 10.7150/thno.21603 -
Cell Metabolism Oct 2019The discovery of prolyl hydroxylase domain proteins (PHDs) as key enzymes in the hypoxia inducible factor (HIF) pathway has been followed by reports of a multitude of...
The discovery of prolyl hydroxylase domain proteins (PHDs) as key enzymes in the hypoxia inducible factor (HIF) pathway has been followed by reports of a multitude of non-HIF substrates of PHD. Reporting in eLife, Cockman et al. (2019) find a surprising lack of detectable PHD activity toward any of them.
Topics: Ankyrin Repeat; Humans; Hydroxylation; Hypoxia; Procollagen-Proline Dioxygenase; Proteomics
PubMed: 31577931
DOI: 10.1016/j.cmet.2019.08.008 -
Biomolecules Jun 2021Ankyrin repeat proteins are found in all three kingdoms of life. Fundamentally, these proteins are involved in protein-protein interaction in order to activate or... (Review)
Review
Ankyrin repeat proteins are found in all three kingdoms of life. Fundamentally, these proteins are involved in protein-protein interaction in order to activate or suppress biological processes. The basic architecture of these proteins comprises repeating modules forming elongated structures. Due to the lack of long-range interactions, a graded stability among the repeats is the generic properties of this protein family determining both protein folding and biological function. Protein folding intermediates were frequently found to be key for the biological functions of repeat proteins. In this review, we discuss most recent findings addressing this close relation for ankyrin repeat proteins including DARPins, Notch receptor ankyrin repeat domain, IκBα inhibitor of NFκB, and CDK inhibitor p19. The role of local folding and unfolding and gradual stability of individual repeats will be discussed during protein folding, protein-protein interactions, and post-translational modifications. The conformational changes of these repeats function as molecular switches for biological regulation, a versatile property for modern drug discovery.
Topics: Animals; Ankyrin Repeat; Biological Phenomena; Humans; Protein Folding; Protein Stability; Protein Structure, Secondary
PubMed: 34198779
DOI: 10.3390/biom11060840 -
Trends in Biochemical Sciences Jan 2019Ankyrin repeat and suppressor of cytokine signaling (SOCS) box (Asb) proteins are ubiquitin E3 ligases. The subfamily of six-ankyrin repeat domain-containing Asb... (Review)
Review
Ankyrin repeat and suppressor of cytokine signaling (SOCS) box (Asb) proteins are ubiquitin E3 ligases. The subfamily of six-ankyrin repeat domain-containing Asb proteins (Asb5, Asb9, Asb11, and Asb13) is of specific interest because they display unusual strong evolutionary conservation (e.g., urochordate and human ASB11 are >49% similar at the amino acid level) and mediate compartment size expansion, regulating, for instance, the size of the brain and muscle compartment. Thus, they may be involved in the explanation of the differences in brain size between humans and apes. Mechanistically, many questions remain, but it has become clear that regulation of canonical Notch signaling and also mitochondrial function are important effectors. Here, we review the action and function of six ankyrin repeat domain-containing Asb proteins in physiology and pathophysiology.
Topics: Animals; Ankyrins; Humans; Signal Transduction; Suppressor of Cytokine Signaling Proteins; Ubiquitin-Protein Ligases
PubMed: 30446376
DOI: 10.1016/j.tibs.2018.10.003 -
Development (Cambridge, England) Jan 2018Developmental biology research would benefit greatly from tools that enable protein function to be regulated, both systematically and in a precise spatial and temporal... (Review)
Review
Developmental biology research would benefit greatly from tools that enable protein function to be regulated, both systematically and in a precise spatial and temporal manner, In recent years, functionalized protein binders have emerged as versatile tools that can be used to target and manipulate proteins. Such protein binders can be based on various scaffolds, such as nanobodies, designed ankyrin repeat proteins (DARPins) and monobodies, and can be used to block or perturb protein function in living cells. In this Primer, we provide an overview of the protein binders that are currently available and highlight recent progress made in applying protein binder-based tools in developmental and synthetic biology.
Topics: Animals; Ankyrin Repeat; Developmental Biology; Humans; Models, Molecular; Peptide Library; Protein Binding; Protein Modification, Translational; Protein Transport; Proteins; Proteolysis; Single-Domain Antibodies; Synthetic Biology
PubMed: 29374062
DOI: 10.1242/dev.148874 -
Molecules (Basel, Switzerland) Jan 2022Ankyrin is one of the most abundant protein repeat families found across all forms of life. It is found in a variety of multi-domain and single domain proteins in humans...
Ankyrin is one of the most abundant protein repeat families found across all forms of life. It is found in a variety of multi-domain and single domain proteins in humans with diverse number of repeating units. They are observed to occur in several functionally diverse proteins, such as transcriptional initiators, cell cycle regulators, cytoskeletal organizers, ion transporters, signal transducers, developmental regulators, and toxins, and, consequently, defects in ankyrin repeat proteins have been associated with a number of human diseases. In this study, we have classified the human ankyrin proteins into clusters based on the sequence similarity in their ankyrin repeat domains. We analyzed the amino acid compositional bias and consensus ankyrin motif sequence of the clusters to understand the diversity of the human ankyrin proteins. We carried out network-based structural analysis of human ankyrin proteins across different clusters and showed the association of conserved residues with topologically important residues identified by network centrality measures. The analysis of conserved and structurally important residues helps in understanding their role in structural stability and function of these proteins. In this paper, we also discuss the significance of these conserved residues in disease association across the human ankyrin protein clusters.
Topics: Ankyrin Repeat; Ankyrins; Databases, Protein; Humans
PubMed: 35056738
DOI: 10.3390/molecules27020423 -
International Journal of Molecular... May 2023Affibodies and designed ankyrin repeat proteins (DARPins) are synthetic proteins originally derived from the virulence factor protein A and the human ankyrin repeat... (Review)
Review
Affibodies and designed ankyrin repeat proteins (DARPins) are synthetic proteins originally derived from the virulence factor protein A and the human ankyrin repeat proteins, respectively. The use of these molecules in healthcare has been recently proposed as they are endowed with biochemical and biophysical features heavily demanded to target and fight diseases, as they have a strong binding affinity, solubility, small size, multiple functionalization sites, biocompatibility, and are easy to produce; furthermore, impressive chemical and thermal stability can be achieved. especially when using affibodies. In this sense, several examples reporting on affibodies and DARPins conjugated to nanomaterials have been published, demonstrating their suitability and feasibility in nanomedicine for cancer therapy. This minireview provides a survey of the most recent studies describing affibody- and DARPin-conjugated zero-dimensional nanomaterials, including inorganic, organic, and biological nanoparticles, nanorods, quantum dots, liposomes, and protein- and DNA-based assemblies for targeted cancer therapy in vitro and in vivo.
Topics: Humans; Designed Ankyrin Repeat Proteins; Proteins; Neoplasms; Nanostructures
PubMed: 37240041
DOI: 10.3390/ijms24108680 -
Plant Cell Reports Feb 2021The ankyrin repeat-containing protein MdANK2B was identified to contribute to increasing resistance to salt stress and decreasing sensitivity to ABA in Malus domestica....
The ankyrin repeat-containing protein MdANK2B was identified to contribute to increasing resistance to salt stress and decreasing sensitivity to ABA in Malus domestica. Ankyrin (ANK) repeat-containing proteins occur widely in prokaryotes, eukaryotes, and even in some viruses and play a critical role in plant growth and development, as well as the response to biotic and abiotic stress. However, the function of ANK repeat-containing proteins in apple (Malus domestica) has not yet been investigated. Here, we identified apple MdANK2B based on homology analysis with the Arabidopsis ANK repeat-containing proteins AtAKR2A and AtAKR2B. MdANK2B was found to be localized in the cytoplasm, and its encoding gene was highly expressed in both apple leaves and fruits. In addition, MdANK2B gene expression was highly induced by salt stresses and abscisic acid (ABA). Overexpression of MdANK2B increased resistance to salt stress and decreased sensitivity to ABA in both transgenic apple calli and seedlings. In addition, overexpression of MdANK2B reduced the accumulation of reactive oxygen species (ROS) by enhancing the activity of antioxidant enzymes in response to salt stress. Our data revealed the role of MdANK2B in response to salt stress and ABA treatment in apple, which widens the known functions of ANK repeat-containing proteins in response to abiotic stress.
Topics: Abscisic Acid; Ankyrin Repeat; Arabidopsis Proteins; Gene Expression; Malus; Molecular Chaperones; Plant Growth Regulators; Plant Proteins; Reactive Oxygen Species; Salt Stress; Salt Tolerance; Stress, Physiological
PubMed: 33331953
DOI: 10.1007/s00299-020-02642-9