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molecular chaperone

Ipsita Subudhi, James Shorter
Ubiquilin 2 (UBQLN2) is an amyotrophic lateral sclerosis-linked molecular chaperone with a prion-like domain that directly engages ubiquitin to triage clients for proteasomal degradation. Dao et al. (2018) now establish that UBQLN2 forms ubiquitin-labile liquids, which may enable UBQLN2 to specifically extract ubiquitylated clients from stress granules for degradation.
March 15, 2018: Molecular Cell
Sebastian Hiller, Björn M Burmann
Living cells contain molecular chaperones that are organized in intricate networks to surveil protein homeostasis by avoiding polypeptide misfolding, aggregation, and the generation of toxic species. In addition, cellular chaperones also fulfill a multitude of alternative functionalities: transport of clients towards a target location, help them fold, unfold misfolded species, resolve aggregates, or deliver clients towards proteolysis machineries. Until recently, the only available source of atomic resolution information for virtually all chaperones were crystal structures of their client-free, apo-forms...
April 2018: Journal of Magnetic Resonance
Geng Li, Chenhui He, Peixuan Bu, Huimin Bi, Sichen Pan, Ronghua Sun, Xin Sheng Zhao
Skp and SurA are both periplasmic chaperones involved in the biogenesis of E. coli β-barrel outer membrane proteins (OMPs). It is commonly assumed that SurA plays a major role, whereas Skp is a minor factor. However, there is no molecular evidence for whether their roles are redundant or not. Here, by using different dilution methods, we obtained monodisperse and aggregated forms of OmpC and studied their interactions with Skp and SurA by single-molecule fluorescence resonance energy transfer (smFRET) and fluorescence correlation spectroscopy (FCS)...
March 15, 2018: ACS Chemical Biology
Glenn T Werneburg, David G Thanassi
Gram-negative bacteria assemble a variety of surface structures, including the hair-like organelles known as pili or fimbriae. Pili typically function in adhesion and mediate interactions with various surfaces, with other bacteria, and with other types of cells such as host cells. The chaperone/usher (CU) pathway assembles a widespread class of adhesive and virulence-associated pili. Pilus biogenesis by the CU pathway requires a dedicated periplasmic chaperone and integral outer membrane protein termed the usher, which forms a multifunctional assembly and secretion platform...
March 2018: EcoSal Plus
Yingjie Miao, Guotong Xiong, Ruoyun Li, Zufang Wu, Xin Zhang, Peifang Weng
Issatchenkia orientalis, a non-Saccharomyces yeast that can resist a wide variety of environmental stresses, has potential use in winemaking and bioethanol production. Little is known about gene expression or the physiology of I. orientalis under ethanol stress. In this study, high-throughput RNA sequencing was used to investigate the transcriptome profile of I. orientalis in response to ethanol. 502 gene transcripts were differentially expressed, of which 451 were more abundant, and 51 less abundant, in cells subjected to 4 h of ethanol stress (10% v/v)...
March 13, 2018: AMB Express
V Z Nezametdinova, D A Mavletova, M G Alekseeva, M S Chekalina, N V Zakharevich, V N Danilenko
The objective of this study was to determine for phosphorylated substrates of the species-specific serine-threonine protein kinase (STPK) Pkb2 from Bifidobacterium longum subsp. longum GT15. Two approaches were employed: analyses of phosphorylated membrane vesicles protein spectra following kinase reactions and analyses of the genes surrounding pkb2. A bioinformatics analysis of the genes surrounding pkb2 found a species-specific gene cluster PFNA in the genomes of 34 different bifidobacterial species. The identified cluster consisted of 5-8 genes depending on the species...
March 10, 2018: Anaerobe
Francesco Spinelli, Ahmed Haider, Annamaria Toscano, Maria Laura Pati, Claudia Keller, Francesco Berardi, Nicola Antonio Colabufo, Carmen Abate, Simon M Ametamey
The Sigma-1 receptor (Sig-1R) has been described as a pluripotent modulator of distinct physiological functions and its involvement in various central and peripheral pathological disorders has been demonstrated. However, further investigations are required to understand the complex role of the Sig-1R as a molecular chaperon. A specific PET radioligand would provide a powerful tool in Sig-1R related studies. As part of our efforts to develop a Sig-1R PET radioligand that shows antagonistic properties, we investigated the suitability of 1-(4-(6-methoxynaphthalen-1-yl)butyl)-4-methylpiperidine (designated PB212) for imaging Sig-1R...
2018: American Journal of Nuclear Medicine and Molecular Imaging
Rakshak Kumar, Vishal Acharya, Srijana Mukhia, Dharam Singh, Sanjay Kumar
Pseudomonas frederiksbergensis ERDD5:01 is a psychrotrophic bacteria isolated from the glacial stream flowing from East Rathong glacier in Sikkim Himalaya. The strain showed survivability at high altitude stress conditions like freezing, frequent freeze-thaw cycles, and UV-C radiations. The complete genome of 5,746,824 bp circular chromosome and a plasmid of 371,027 bp was sequenced to understand the genetic basis of its survival strategy. Multiple copies of cold-associated genes encoding cold active chaperons, general stress response, osmotic stress, oxidative stress, membrane/cell wall alteration, carbon storage/starvation and, DNA repair mechanisms supported its survivability at extreme cold and radiations corroborating with the bacterial physiological findings...
March 9, 2018: Genomics
Susana Cedrés, Enriqueta Felip, Cristina Cruz, Ana Martinez de Castro, Nuria Pardo, Alejandro Navarro, Alex Martinez-Marti, Jordin Remon, Jorge Zeron-Medina, Judith Balmaña, Alba Llop-Guevara, Josep M Miquel, Irene Sansano, Paolo Nuciforo, Francesco Mancuso, Violeta Serra, Ana Vivancos
Heat shock proteins (HSPs) are molecular chaperones that maintain proteins in their correct conformation to ensure stability and protect carcinoma cells from apoptosis. HSP90 inhibitors (HSP90i) block multiple targets simultaneously, and despite responses in a selected population, no HSP90i have yet been approved. We present a patient with a lung tumor with an exceptional response to cisplatin/gemcitabine in combination with HSP90i, which nowadays continues with HSP90i maintenance after three years. Whole-exome sequencing of the lung tumor unveiled a BRCA1/2 deficiency mutational signature, and mutation analysis confirmed a germline BRCA1 mutation...
February 26, 2018: Journal of the National Cancer Institute
Paolo Ruzza, Rosa Maria Vitale, Rohanah Hussain, Alessia Montini, Claudia Honisch, Alice Pozzebon, Charlotte S Hughes, Barbara Biondi, Pietro Amodeo, GianPietro Sechi, Giuliano Siligardi
BACKGROUND: Lysozyme is a widely distributed enzyme present in a variety of tissue and body fluids. Human and hen egg white lysozyme are used as validated model to study protein folding and stability and to understand protein misfolding and aggregation. We recently found that ceftriaxone, a β-lactam antibiotic able to overcome the blood-brain barrier, successfully eliminated the cellular toxic effects of misfolded proteins as Glial Fibrillary Acidic Protein and α-synuclein. To further understand the anti-amyloidogenic properties of ceftriaxone, we studied its activity towards lysozyme aggregation with the aim to investigate a possible chaperone-like activity of this molecule...
March 7, 2018: Biochimica et Biophysica Acta
Z Wyżewski, K P Gregorczyk, J Szczepanowska, L Szulc-Dąbrowska
Heat shock proteins (Hsps) are a family of proteins highly conserved in evolution. Members of the Hsp family are mainly responsible for proper protein folding, however they perform many other functions in living organisms. Hsp60 is a molecular chaperone that is present in mitochondria and cytosol of eukaryotic cells, as well as on their surface. It is also found in the extracellular space and in the peripheral blood. Apart from its role in assisting protein folding in cooperation with Hsp10, Hsp60 contributes to regulation of apoptosis, as well as participates in modulation of the immune system activity...
2018: Acta Virologica
Maria Adell, Bárbara M Calisto, Ignacio Fita, Luca Martinelli
Hsp70 chaperones keep protein homeostasis facilitating the response of organisms to changes in external and internal conditions. Hsp70s have two domains - Nucleotide Binding Domain (NBD) and Substrate Binding Domain (SBD) - connected by a conserved hydrophobic linker. Functioning of Hsp70s depend on tightly regulated cycles of ATP hydrolysis allosterically coupled, often together with co-chaperones, to the binding/release of peptide substrates. Here we describe the crystal structure of the Mycoplasma genitalium DnaK (MgDnaK) protein, an Hsp70 homolog, in the non-compact, nucleotide-bound/substrate-bound conformation...
March 9, 2018: Protein Science: a Publication of the Protein Society
Blagojce Jovcevski, J Andrew Aquilina, Justin L P Benesch, Heath Ecroyd
αB-Crystallin (HSPB5) is a small heat-shock protein that is composed of dimers that then assemble into a polydisperse ensemble of oligomers. Oligomerisation is mediated by heterologous interactions between the C-terminal tail of one dimer and the core "α-crystallin" domain of another and stabilised by interactions made by the N-terminal region. Comparatively little is known about the latter contribution, but previous studies have suggested that residues in the region 54-60 form contacts that stabilise the assembly...
March 8, 2018: Cell Stress & Chaperones
Sander Bekeschus, Jan-Wilm Lackmann, Denis Gümbel, Matthias Napp, Anke Schmidt, Kristian Wende
Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates...
March 7, 2018: International Journal of Molecular Sciences
Taewook Kang, Pia Jensen, Vita Solovyeva, Jonathan R Brewer, Martin R Larsen
Characterization of molecular mechanisms underlying pancreatic β-cell function in relation to glucose-stimulated insulin secretion is incomplete, especially with respect to global response in the nuclear environment. Here, we focus on the characterization of proteins in the nuclear environment of β-cells after brief, high glucose-stimulation. We compared purified nuclei derived from β-cells stimulated with 17mM glucose for 0, 2, and 5 minutes using quantitative proteomics, a time frame that most likely does not result in translation of new protein in the cell...
March 8, 2018: Journal of Proteome Research
Xinwei Yang, Chongrong Ke, Jiangming Zhu, Yan Wang, Wenchao Zeng, Jianzhong Huang
We previously developed a gamma-amino butyric acid (GABA)-producing strain of Escherichia coli, leading to production of 614.15 g/L GABA at 45 °C from L-glutamic acid (L-Glu) with a productivity of 40.94 g/L/h by three successive whole-cell conversion cycles. However, the increase in pH caused by the accumulation of GABA resulted in inactivation of the biocatalyst and consequently led to relatively lower productivity. In this study, by overcoming the major problem associated with the increase in pH during the production process, a more efficient biocatalyst was obtained through cascade modifications of the previously reported E...
March 7, 2018: Applied Microbiology and Biotechnology
Padmavathi A V Thangella, Srinivas N B S Pasumarti, Raghu Pullakhandam, Bhanuprakash Reddy Geereddy, Manohar Rao Daggu
Drought is a major constraint to the productivity of many crops affecting various physiological and biochemical processes. Seventy percent of the peanuts are grown in semiarid tropics that are frequently prone to drought stress. So, we analyzed its effect in 4 cultivars of peanut, with different degrees of drought tolerance, under 10 and 20 days of water stress using two-dimensional gel electrophoresis and mass spectrometry. A total of 189 differentially expressed protein spots were identified in the leaf proteome of all the 4 cultivars using PD Quest Basic software; 74 in ICGV 91114, 41 in ICGS 76, 44 in J 11 and 30 in JL 24...
March 2018: 3 Biotech
Zahra Assur Sanghai, Linamarie Miller, Kelly R Molloy, Jonas Barandun, Mirjam Hunziker, Malik Chaker-Margot, Junjie Wang, Brian T Chait, Sebastian Klinge
Early co-transcriptional events of eukaryotic ribosome assembly result in the formation of precursors of the small (40S) and large (60S) ribosomal subunits1 . A multitude of transient assembly factors regulate and chaperone the systematic folding of pre-ribosomal RNA subdomains. However, due to limited structural information, the role of these factors during early nucleolar 60S assembly is not fully understood. Here we have determined cryo-EM reconstructions of the nucleolar pre-60S ribosomal subunit in different conformational states at resolutions up to 3...
March 5, 2018: Nature
V V Marchenkov, N V Kotova, T A Muranova, G V Semisotnov
GroES is a heptameric partner of tetradecameric molecular chaperone GroEL, which ensures the correct folding and assembly of numerous cellular proteins both in vitro and in vivo. This work demonstrates the results of a study of structural aspects of GroES that affect its interaction with GroEL and reassembly. The effect of limited trypsinolysis of GroES on these processes has been studied. It has been shown that limited trypsinolysis of GroES is only strongly pronounced outside the complex with GroEL and results in the cleavage of the peptide bond between Lys20 and Ser21...
January 2018: Molekuliarnaia Biologiia
Toshimi Michigami
Congenital skeletal dysplasias have been considered to be fundamentally untreatable diseases. However, molecular diagnosis by genetic testing has become more prevalent, and efforts are being made to develop novel therapies based on the pathogenesis. As treatments for osteogenesis imperfecta, in addition to anti-resorptive agents, neutralizing antibodies against sclerostin and transforming growth factor(TGF)-β and chemical chaperones can be beneficial. Enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has been recently developed to treat hypophosphatasia and has much improved the prognosis of the patients affected with severe forms of the disease...
2018: Clinical Calcium
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