journal
https://read.qxmd.com/read/38759730/s100a4-makes-two-appearances-in-mechanisms-leading-to-fibrosis
#1
JOURNAL ARTICLE
László Nyitray
Non-muscle myosin 2 (NM2) is known to play an important role in myofibroblast transdifferentiation, a hallmark of fibrotic disorders. In a recent JBC article, Southern et al. demonstrate that endogenous S100A4, a calcium- and NM2-binding protein acts as a mechanoeffector in this process. Since extracellular S100A4 is also involved in fibrogenesis by triggering the inflammatory response, this small protein appears to contribute to fibrosis via at least two distinct mechanisms.
May 15, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38754781/cardioprotective-properties-of-omt-28-a-synthetic-analog-of-omega-3-epoxyeicosanoids
#2
JOURNAL ARTICLE
Joshua Kranrod, Anne Konkel, Robert Valencia, Ahmed Darwesh, Robert Fischer, Wolf-Hagen Schunck, John M Seubert
OMT-28 is a metabolically robust small molecule developed to mimic the structure and function of omega-3 epoxyeicosanoids. However, it remained unknown to what extent OMT-28 also shares the cardio-protective and anti-inflammatory properties of its natural counterparts. To address this question, we analyzed the ability of OMT-28 to ameliorate hypoxia/reoxygenation (HR)-injury and lipopolysaccharide (LPS)-induced endotoxemia in cultured cardiomyocytes. Moreover, we investigated the potential of OMT-28 to limit functional damage and inflammasome activation in isolated perfused mouse hearts subjected to ischemia/reperfusion (IR) injury...
May 14, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38749156/correction-selective-targeting-and-clustering-of-phosphatidylserine-lipids-by-rsv-m-protein-is-critical-for-virus-particle-production
#3
Jitendriya Swain, Maxime Bierre, Laura Veyrié, Charles-Adrien Richard, Jean-Francois Eleouet, Delphine Muriaux, Monika Bajorek
No abstract text is available yet for this article.
May 14, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38750796/kinetic-comparison-of-all-eleven-viral-polyprotein-cleavage-site-processing-events-by-sars-cov-2-main-protease-using-a-linked-protein-fret-platform
#4
JOURNAL ARTICLE
Calem Kenward, Marija Vuckovic, Mark Paetzel, Natalie C J Strynadka
The main protease (Mpro ) remains an essential therapeutic target for COVID-19 post infection intervention given its critical role in processing the majority of viral proteins encoded by the genome of SARS-CoV-2. Upon viral entry, the +ssRNA genome is translated into two long polyproteins (pp1a or the frameshift-dependent pp1ab) containing all the non-structural proteins (nsps) required by the virus for immune modulation, replication, and ultimately, virion assembly. Included among these nsps is the cysteine protease Mpro (nsp5) which self-excises from the polyprotein, dimerizes, then consecutively cleaves 11 of the 15 cut site junctions found between each nsp within the polyprotein...
May 13, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38750795/evolutionary-insights-into-sequence-modifications-governing-chitin-recognition-and-chitinase-inactivity-in-ykl-40-hc-gp39-chi3l1
#5
JOURNAL ARTICLE
Keita Suzuki, Kazuaki Okawa, Masashi Ohkura, Tomoki Kanaizumi, Takaki Kobayashi, Koro Takahashi, Hiromu Takei, Momo Otsuka, Eri Tabata, Peter O Bauer, Fumitaka Oyama
YKL-40, also known as human cartilage glycoprotein-39 (HC-gp39) or CHI3L1, shares structural similarities with chitotriosidase (CHIT1), an active chitinase, but lacks chitinase activity. Despite being a biomarker for inflammatory disorders and cancer, the reasons for YKL-40's inert chitinase function have remained elusive. This study reveals that the loss of chitinase activity in YKL-40 has risen from multiple sequence modifications influencing its chitin affinity. Contrary to the common belief associating the lack of chitinase activity with amino acid substitutions in the catalytic motif, attempts to activate YKL-40 by creating two amino acid mutations in the catalytic motif (MT-YKL-40) proved ineffective...
May 13, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38750794/polymerization-mechanism-of-the-candida-albicans-virulence-factor-candidalysin
#6
JOURNAL ARTICLE
Katherine G Schaefer, Charles M Russell, Robert J Pyron, Elizabeth A Conley, Francisco N Barrera, Gavin M King
Candida albicans is a commensal fungus that can cause epithelial infections and life-threatening invasive candidiasis. The fungus secretes candidalysin (CL), a peptide that causes cell damage and immune activation by permeation of epithelial membranes. The mechanism of CL action involves strong peptide assembly into polymers in solution. The free ends of linear CL polymers can join, forming loops that become pores upon binding to membranes. CL polymers constitute a therapeutic target for candidiasis, but little is known about CL self-assembly in solution...
May 13, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38750793/ascc1-structures-and-bioinformatics-reveal-a-novel-helix-clasp-helix-rna-binding-motif-linked-to-a-two-histidine-phosphodiesterase
#7
JOURNAL ARTICLE
Naga Babu Chinnam, Roopa Thapar, Andrew S Arvai, Altaf H Sarker, Jennifer M Soll, Tanmoy Paul, Aleem Syed, Daniel J Rosenberg, Michal Hammel, Albino Bacolla, Panagiotis Katsonis, Abhishek Asthana, Miaw-Sheue Tsai, Ivaylo Ivanov, Olivier Lichtarge, Robert H Silverman, Nima Mosammaparast, Susan E Tsutakawa, John A Tainer
Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 complex in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient domains: nucleotide-binding K-Homology (KH) (associated with regulating splicing, transcriptional, and translation) and two-histidine phosphodiesterase (PDE) (associated with hydrolysis of cyclic nucleotide phosphate bonds). Germline mutations link loss of ASCC1 function to spinal muscular atrophy with congenital bone fractures 2 (SMABF2). Herein analysis of The Cancer Genome Atlas (TCGA) suggests ASCC1 RNA overexpression in certain tumors correlates with poor survival, Signatures 29 and 3 mutations, and genetic instability markers...
May 13, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38750792/crystal-structure-of-the-photosensory-module-from-a-pas-less-cyanobacterial-phytochrome-as-pr-shows-a-mix-of-dark-adapted-and-photoactivated-features
#8
JOURNAL ARTICLE
E Sethe Burgie, Alayna J Mickles, Fang Luo, Mitchell D Miller, Richard D Vierstra
Phytochromes (Phys) are a diverse collection of photoreceptors that regulate numerous physiological and developmental processes in microorganisms and plants through photointerconversion between red-light absorbing Pr and far-red light-absorbing Pfr states. Light is detected by an N-terminal photosensing module (PSM) sequentially comprised of Period/ARNT/Sim (PAS), cGMP-phosphodiesterase/adenylyl cyclase/FhlA (GAF), and Phy-specific (PHY) domains, with the bilin chromophore covalently-bound within the GAF domain...
May 13, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38750791/bacterial-cysteate-dissimilatory-pathway-involves-a-racemase-and-d-cysteate-sulfo-lyase
#9
JOURNAL ARTICLE
Chunxiu Liu, Kailiang Ma, Li Jiang, Xumei Liu, Yang Tong, Sen Yang, Xinghua Jin, Yifeng Wei, Yan Zhang
The sulfite-reducing bacterium Bilophila wadsworthia, a common human intestinal pathobiont, is unique in its ability to metabolize a wide variety of sulfonates to generate sulfite as a terminal electron acceptor (TEA). The resulting formation of H2 S is implicated in inflammation and colon cancer. l-cysteate, an oxidation product of l-cysteine, is among the sulfonates metabolized by B. wadsworthia, although the enzymes involved remain unknown. Here we report a pathway for l-cysteate dissimilation in B. wadsworthia RZATAU, involving isomerization of l-cysteate to d-cysteate by a cysteate racemase (BwCuyB), followed by cleavage into pyruvate, ammonia and sulfite by a d-cysteate sulfo-lyase (BwCuyA)...
May 13, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38750790/leishmania-exploits-host-camp-epac-calcineurin-signaling-to-induce-an-il-33-mediated-anti-inflammatory-environment-for-the-establishment-of-infection
#10
JOURNAL ARTICLE
Souravi Roy, Shalini Roy, Satyajit Halder, Kuladip Jana, Anindita Ukil
Host anti-inflammatory responses are critical for the progression of visceral leishmaniasis and the pleomorphic cytokine IL-33 was found to be upregulated in infection. The underlying mechanism is not yet known. Here, we documented that IL-33 induction is a consequence of elevated cAMP-mediated EPAC/calcineurin-dependent signaling and is essential for the sustenance of infection. L. donovani-infected RAW and bone marrow-derived macrophages showed significant up-regulation of IL-33 and its neutralization by anti-IL-33 antibody resulted in decreased parasite survival and increased inflammatory responses...
May 13, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38735479/a-tribute-to-sidney-altman-one-of-the-architects-of-modern-rna-biology
#11
JOURNAL ARTICLE
Venkat Gopalan, Leif A Kirsebom
This special issue of JBC pays tribute to Sidney Altman, whose discovery of a catalytic role for RNA, a breakthrough made independently by Thomas Cech, overturned the long-held dogma that only proteins can serve as catalysts in biological systems. The discovery of RNA catalysis galvanized biologists to think expansively in new directions and has given rise to a remarkable RNAissance in science and medicine. The collection of articles begins with the story of the discovery of RNase P and builds up to the emerging picture of an unexpectedly vast repertoire of RNase P variants in the three domains of life, including insights derived from recent high-resolution structures on how RNAs, ribonucleoproteins, or protein scaffolds can be used variably to generate an active site for catalyzing the same RNA processing reaction...
May 10, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38735478/bayesian-network-models-identify-cooperative-gpcr-g-protein-interactions-that-contribute-to-g-protein-coupling
#12
JOURNAL ARTICLE
Elizaveta Mukhaleva, Ning Ma, Wijnand J C van der Velden, Grigoriy Gogoshin, Sergio Branciamore, Supriyo Bhattacharya, Andrei S Rodin, Nagarajan Vaidehi
Cooperative interactions in protein-protein interfaces demonstrate the interdependency or the linked network- like behavior and their effect on the coupling of proteins. Cooperative interactions also could cause ripple or allosteric effects at a distance in protein-protein interfaces. Although they are critically important in protein-protein interfaces, it is challenging to determine which amino acid pair interactions are cooperative. In this work we have used Bayesian network modeling, an interpretable machine learning method, combined with molecular dynamics trajectories to identify the residue pairs that show high cooperativity and their allosteric effect in the interface of G protein coupled receptor (GPCR) complexes with Gα subunits...
May 10, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38735477/non-specific-n-terminal-tetrapeptide-insertions-disrupt-the-translation-arrest-induced-by-ribosome-arresting-peptide-sequences
#13
JOURNAL ARTICLE
Akinano Kobo, Hideki Taguchi, Yuhei Chadani
The nascent polypeptide chains passing through the ribosome tunnel not only serve as an intermediate of protein synthesis but also, in some cases, act as dynamic genetic information, controlling translation through interaction with the ribosome. One notable example is Escherichia coli SecM, in which translation of the ribosome arresting peptide (RAP) sequence in SecM leads to robust elongation arrest. Translation regulations, including the SecM-induced translation arrest, play regulatory roles such as gene expression control...
May 10, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38735476/enzyme-cargo-encapsulation-peptides-bind-between-tessellating-tiles-of-the-bacterial-microcompartment-shell
#14
JOURNAL ARTICLE
Shuang Gu, Jack Bradley-Clarke, Ruth-Sarah Rose, Martin J Warren, Richard W Pickersgill
Bacterial microcompartments are prokaryotic organelles comprising encapsulated enzymes within a thin protein shell. They facilitate metabolic processing including propanediol, choline, glycerol, and ethanolamine utilization, and they accelerate carbon fixation in cyanobacteria. Enzymes targeted to the inside of the microcompartment frequently possess a cargo-encapsulation peptide, but the site to which the peptide binds is unclear. We provide evidence that the encapsulation peptides bind to the hydrophobic groove formed between tessellating subunits of the shell proteins...
May 10, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38735475/bridging-the-maytansine-and-vinca-sites-cryptophycins-target-%C3%AE-tubulin-s-t5-loop
#15
JOURNAL ARTICLE
Anne-Catherine Abel, Tobias Mühlethaler, Cedric Dessin, Thomas Schachtsiek, Benedikt Sammet, Timothy Sharpe, Michel O Steinmetz, Norbert Sewald, Andrea E Prota
Cryptophycins are microtubule-targeting agents (MTAs) that belong to the most potent antimitotic compounds known to date; however, their exact molecular mechanism of action remains unclear. Here, we present the 2.2 Å resolution X-ray crystal structure of a potent cryptophycin derivative bound to the αβ-tubulin heterodimer. The structure addresses conformational issues present in a previous 3.3 Å resolution cryo-electron microscopy structure of cryptophycin-52 bound to the maytansine site of β-tubulin...
May 10, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38735474/foxk2-targeting-by-the-scf-e3-ligase-subunit-fbxo24-for-ubiquitin-mediated-degradation-modulates-mitochondrial-respiration
#16
JOURNAL ARTICLE
Rabab El-Mergawy, Lexie Chafin, Jose A Ovando-Ricardez, Lorena Rosa, MuChun Tsai, Mauricio Rojas, Ana L Mora, Rama K Mallampalli
FOXK2 is a crucial transcription factor implicated in a wide array of biological activities and yet understanding of its molecular regulation at the level of protein turnover is limited. Here we identify that FOXK2 undergoes degradation in lung epithelia in the presence of the virulent pathogens P. aeruginosa and K. pneumoniae through ubiquitin-proteasomal processing. FOXK2 through its carboxyl-terminus (aa 428-478) binds the Skp-Cullin-F-box ubiquitin E3 ligase subunit FBXO24 that mediates multisite polyubiquitylation of the transcription factor resulting in its nuclear degradation...
May 10, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38735473/sugar-ring-alignment-and-dynamics-underline-cytarabine-and-gemcitabine-inhibition-on-pol-%C3%AE-catalyzed-dna-synthesis
#17
JOURNAL ARTICLE
Caleb Chang, Grace Zhou, Christie Lee Luo, Sarah Eleraky, Madeline Moradi, Yang Gao
Nucleoside analogue drugs are pervasively used as antiviral and chemotherapy agents. Cytarabine and gemcitabine are anti-cancer nucleoside analogue drugs that contain C2´ modifications on the sugar ring. Despite carrying all the required functional groups for DNA synthesis, these two compounds inhibit DNA extension once incorporated into DNA. It remains unclear how the C2´ modifications on cytarabine and gemcitabine affect the polymerase active site during substrate binding and DNA extension. Using steady-state kinetics, static and time-resolved X-ray crystallography with DNA polymerase η (Pol η) as a model system, we showed that the sugar ring C2´ chemical groups on cytarabine and gemcitabine snugly fit within the Pol η active site without occluding the steric gate...
May 10, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38723751/biochemical-and-functional-characterization-of-the-p-a165t-missense-variant-of-mitochondrial-amidoxime-reducing-component-1
#18
JOURNAL ARTICLE
Wangfang Hou, Christian Watson, Ted Cecconie, Menaka N Bolaki, Jennifer J Brady, Quinn Lu, Gregory J Gatto, Tovah A Day
Recent genome-wide association studies have identified a missense variant p.A165T in mitochondrial amidoxime-reducing component 1 (mARC1) that is strongly associated with protection from all-cause cirrhosis and improved prognosis in nonalcoholic steatohepatitis (NASH). The precise mechanism of this protective effect is unknown. Substitution of alanine 165 with threonine is predicted to affect mARC1 protein stability and to have deleterious effects on its function. To investigate the mechanism, we have generated a knock-in mutant mARC1 A165T and a catalytically dead mutant C273A (as a control) in human hepatoma HepG2 cells, enabling characterization of protein subcellular distribution, stability, and biochemical functions of the mARC1 mutant protein expressed from its endogenous locus...
May 7, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38723750/fructose-1-kinase-has-pleiotropic-roles-in-escherichia-coli
#19
JOURNAL ARTICLE
Chamitha Weeramange, Cindy Menjivar, Pierce T O'Neil, Samir El Qaidi, Kelly S Harrison, Sarah Meinhardt, Cole L Bird, Shwetha Sreenivasan, Philip R Hardwidge, Aron W Fenton, P Scott Hefty, Jeffrey L Bose, Liskin Swint-Kruse
In Escherichia coli, the master transcription regulator Catabolite Repressor Activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that the E...
May 7, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38718868/stat3-activation-of-scap-srebp-1-signaling-upregulates-fatty-acid-synthesis-to-promote-tumor-growth
#20
JOURNAL ARTICLE
Yunzhou Fan, Rui Zhang, Chao Wang, Meixia Pan, Feng Geng, Yaogang Zhong, Huali Su, Yongjun Kou, Xiaokui Mo, Etienne Lefai, Xianlin Han, Arnab Chakravarti, Deliang Guo
SCAP plays a central role in controlling lipid homeostasis by activating SREBP-1, a master transcription factor in controlling fatty acid (FA) synthesis. However, how SCAP expression is regulated in human cancer cells remains unknown. Here, we revealed that STAT3 binds to the promoter of SCAP to activate its expression across multiple cancer cell types. Moreover, we identified that STAT3 also concurrently interacts with the promoter of SREBF1 gene (encoding SREBP-1), amplifying its expression. This dual action by STAT3 collaboratively heightens FA synthesis...
May 6, 2024: Journal of Biological Chemistry
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