Genomes and Genes
Summary: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
- Shutova M, Asokan S, Talwar S, Assoian R, Bear J, Svitkina T. Self-sorting of nonmuscle myosins IIA and IIB polarizes the cytoskeleton and modulates cell motility. J Cell Biol. 2017;216:2877-2889 pubmed publisher..By copolymerizing with NMIIB, NMIIA accelerates the intrinsically slow NMIIB dynamics, thus increasing cell motility and traction and enabling chemotaxis. ..
- Prusty A, Meduri R, Prusty B, Vanselow J, Schlosser A, Fischer U. Impaired spliceosomal UsnRNP assembly leads to Sm mRNA down-regulation and Sm protein degradation. J Cell Biol. 2017;216:2391-2407 pubmed publisher..Our studies identify an elaborate safeguarding system that prevents individual Sm proteins from aggregating, contributing to cellular UsnRNP homeostasis. ..
- Stevens C, Rayani K, Singh G, Lotfalisalmasi B, Tieleman D, Tibbits G. Changes in the dynamics of the cardiac troponin C molecule explain the effects of Ca2+-sensitizing mutations. J Biol Chem. 2017;292:11915-11926 pubmed publisher..Our data further suggest that modulation of the structural dynamics is the underlying molecular mechanism for many disease mutations that are far from the regulatory Ca2+-binding site of cTnC. ..
- Wang S, Tang L, Lin J, Shen Z, Yao Y, Wang W, et al. ABCB5 promotes melanoma metastasis through enhancing NF-?B p65 protein stability. Biochem Biophys Res Commun. 2017;492:18-26 pubmed publisher..Consequently, ABCB5 activates the NF-?B pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target ..
- Grishin D, Pokrovskaya M, Podobed O, Gladilina J, Pokrovsky V, Aleksandrova S, et al. [Prediction of protein thermostability from their primary structure: the current state and development factors]. Biomed Khim. 2017;63:124-131 pubmed publisher..Osoboe vnimanie udeleno prognosticheskomu potentsialu statisticheskikh metodov izucheniia termodinamicheskikh pokazatele? pervichno? struktury belka i otseneny ikh perspektivy. ..
- Chanda A, Chan A, Deng L, Kornaga E, Enwere E, Morris D, et al. Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer. PLoS ONE. 2017;12:e0177639 pubmed publisher..Our studies thus identify the SUMO E3 ligase PIAS1 as a prognostic biomarker in breast cancer, and suggest a potential role for the PIAS1-SnoN sumoylation pathway in controlling breast cancer metastasis. ..
- Yokoyama T, Hanawa Y, Obita T, Mizuguchi M. Stability and crystal structures of His88 mutant human transthyretins. FEBS Lett. 2017;591:1862-1871 pubmed publisher..Our results suggest that in some cases TTR is destabilized due to alterations in bound water molecules as well as structural changes in TTR itself. ..
- Broom A, Jacobi Z, Trainor K, Meiering E. Computational tools help improve protein stability but with a solubility tradeoff. J Biol Chem. 2017;292:14349-14361 pubmed publisherAccurately predicting changes in protein stability upon amino acid substitution is a much sought after goal...
- Garreau A, Blaize G, Argenty J, Rouquié N, Tourdès A, Wood S, et al. Grb2-Mediated Recruitment of USP9X to LAT Enhances Themis Stability following Thymic Selection. J Immunol. 2017;199:2758-2766 pubmed publisher..Together, these data suggest that TCR-mediated signals enhance Themis stability upon T cell development and identify USP9X as a key regulator of Themis protein turnover. ..
- Winter L, Staszewska I, Mihailovska E, Fischer I, Goldmann W, Schroder R, et al. Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle. J Clin Invest. 2014;124:1144-57 pubmed..Together, these data demonstrate the biological relevance of the MFM cell model and suggest that this model has potential use for the development of therapeutic approaches for EBS-MD. ..
- Nguyen Y, Nguyen N, Rogers J, Liao J, Macmillan J, Jiang Y, et al. Structural and mechanistic roles of novel chemical ligands on the SdiA quorum-sensing transcription regulator. MBio. 2015;6: pubmed publisher..Our studies provide crucial mechanistic insights into the ligand regulation of SdiA activity. ..
- Vig A, Földi I, Szikora S, Migh E, Gombos R, Tóth M, et al. The activities of the C-terminal regions of the formin protein disheveled-associated activator of morphogenesis (DAAM) in actin dynamics. J Biol Chem. 2017;292:13566-13583 pubmed publisher..In conclusion, our results demonstrate that the CT region of DAAM plays an important role in actin assembly regulation in a biological context. ..
- Borkosky S, Camporeale G, Chemes L, Risso M, Noval M, Sánchez I, et al. Hidden Structural Codes in Protein Intrinsic Disorder. Biochemistry. 2017;56:5560-5569 pubmed publisher..Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble. ..
- Li X, Nelson C, Nair R, Hazlehurst L, Moroni T, Martínez Acedo P, et al. Stable and Potent Selenomab-Drug Conjugates. Cell Chem Biol. 2017;24:433-442.e6 pubmed publisher..These site-specific antibody-drug conjugates built on a selenocysteine interface revealed broad therapeutic utility in liquid and solid malignancy models. ..
- Medina Ramirez M, Sanders R, Sattentau Q. Stabilized HIV-1 envelope glycoprotein trimers for vaccine use. Curr Opin HIV AIDS. 2017;12:241-249 pubmed publisher..This review will give a perspective on these challenges, and summarize current approaches to overcoming them with the aim of developing immunogens to elicit bNAb responses in humans by active vaccination. ..
- Sala Rabanal M, Yurtsever Z, Berry K, Nichols C, Brett T. Modulation of TMEM16A channel activity by the von Willebrand factor type A (VWA) domain of the calcium-activated chloride channel regulator 1 (CLCA1). J Biol Chem. 2017;292:9164-9174 pubmed publisher..Our study hints at the therapeutic potential of the selective activation of TMEM16A by the CLCA1 VWA domain in loss-of-function chloride channelopathies such as cystic fibrosis. ..
- Spencer R, Hochbaum A. The Phe-Ile Zipper: A Specific Interaction Motif Drives Antiparallel Coiled-Coil Hexamer Formation. Biochemistry. 2017;56:5300-5308 pubmed publisher..Finally, we expanded on the generality of the Phe-Ile zipper, creating a unique sequence that forms an antiparallel hexamer that is topologically similar to ACC-Hex but atomistically unique...
- Nickless A, Cheruiyot A, Flanagan K, Piwnica Worms D, Stewart S, You Z. p38 MAPK inhibits nonsense-mediated RNA decay in response to persistent DNA damage in noncycling cells. J Biol Chem. 2017;292:15266-15276 pubmed publisher..Our results reveal a novel p38?-dependent pathway that regulates NMD activity in response to persistent DNA damage, which, in turn, controls ATF3 expression in affected cells. ..
- Wang W, Xia Z, FarrÃ© J, Subramani S. TRIM37, a novel E3 ligase for PEX5-mediated peroxisomal matrix protein import. J Cell Biol. 2017;216:2843-2858 pubmed publisher..Therefore, TRIM37-mediated ubiquitylation stabilizes PEX5 and promotes peroxisomal matrix protein import, suggesting that mulibrey nanism is a new PBD. ..
- Taniguchi T, Woodward A, Magnelli P, McColgan N, Lehoux S, Jacobo S, et al. N-Glycosylation affects the stability and barrier function of the MUC16 mucin. J Biol Chem. 2017;292:11079-11090 pubmed publisher..Taken together, these studies define a role for N-linked oligosaccharides in supporting the stability and function of transmembrane mucins on mucosal surfaces. ..
- Londino J, Gulick D, Lear T, Suber T, Weathington N, Masa L, et al. Post-translational modification of the interferon-gamma receptor alters its stability and signaling. Biochem J. 2017;474:3543-3557 pubmed publisher..Ubiquitination appears to be necessary for efficient IFNGR1-dependent gamma gene induction and represents a relatively uncharacterized regulatory mechanism for this receptor. ..
- Ward C, Maselko M, Lupfer C, Prescott M, Pastey M. Interaction of the Human Respiratory Syncytial Virus matrix protein with cellular adaptor protein complex 3 plays a critical role in trafficking. PLoS ONE. 2017;12:e0184629 pubmed publisher..The results of this study add new insights and targets that may lead to the development of potential antivirals and attenuating mutations suitable for candidate vaccines in the future. ..
- Klar J, Ali Z, Farooq M, Khan K, Wikstrom J, Iqbal M, et al. A missense variant in ITPR1 provides evidence for autosomal recessive SCA29 with asymptomatic cerebellar hypoplasia in carriers. Eur J Hum Genet. 2017;25:848-853 pubmed publisher..Our findings add to the genetic complexity of SCA29 and broaden the correlations between ITPR1 variants and their clinical expression. ..
- Moon J, Choi S, Heo C, Kim H, Kim H. Î±-Syntrophin stabilizes catalase to reduce endogenous reactive oxygen species levels during myoblast differentiation. FEBS J. 2017;284:2052-2065 pubmed publisher..This protein plays an important role in the regulation of oxidative stress from endogenously generated ROS during myoblast differentiation by modulating the protein stability of catalase.
- Liang B, Ngwuta J, Surman S, Kabatova B, Liu X, Lingemann M, et al. Improved Prefusion Stability, Optimized Codon Usage, and Augmented Virion Packaging Enhance the Immunogenicity of Respiratory Syncytial Virus Fusion Protein in a Vectored-Vaccine Candidate. J Virol. 2017;91: pubmed publisher..The improved immunogenicity included induction of increased titers of high-quality complement-independent antibodies with greater pre-F site Ã˜ binding and greater protection against RSV challenge. ..
- Hishinuma E, Akai F, Narita Y, Maekawa M, Yamaguchi H, Mano N, et al. Functional characterization of 21 allelic variants of dihydropyrimidinase. Biochem Pharmacol. 2017;143:118-128 pubmed publisher..Thus, detection of DPYS genetic polymorphisms might facilitate the prediction severe adverse effects of fluoropyrimidine-based treatments. ..
- Sulthana S, Quesada E, Deutscher M. RNase II regulates RNase PH and is essential for cell survival during starvation and stationary phase. RNA. 2017;23:1456-1464 pubmed publisher..In the absence of RNase II, RNase PH levels remain high, leading to excessive ribosome loss and ultimately to cell death. These findings provide another example of RNase regulation in response to environmental stress. ..
- McGlinchey R, Dominah G, Lee J. Taking a Bite Out of Amyloid: Mechanistic Insights into ?-Synuclein Degradation by Cathepsin L. Biochemistry. 2017;56:3881-3884 pubmed publisher..The ability of CtsL to degrade ?-syn amyloid fibrils offers a promising strategy for improving the cellular clearance of aggregated ?-syn through the modulation of protease levels and activity. ..
- Chen Y, LaMarche M, Chan H, Fekkes P, García Fortanet J, Acker M, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016;535:148-52 pubmed..Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. ..
- Rietz A, Li H, Quist K, Cherry J, Lorson C, Burnett B, et al. Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy. J Med Chem. 2017;60:4594-4610 pubmed publisher..This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA. ..
- Schumacher M, Zeng W, Findlay K, Buttner M, Brennan R, Tschowri N. The Streptomyces master regulator BldD binds c-di-GMP sequentially to create a functional BldD2-(c-di-GMP)4 complex. Nucleic Acids Res. 2017;45:6923-6933 pubmed publisher..Here, we show that c-di-GMP binds BldD using an ordered, sequential mechanism and that BldD function necessitates the assembly of the BldD2-(c-di-GMP)4 complex. ..
- Erb U, Zhao K, Wang Z, Xiao L, ZÃ¶ller M. Murine and human pancreatic tumor exosome recovery in mouse serum: Diagnostic and prognostic potential and target cell delivery. Cancer Lett. 2017;403:1-12 pubmed publisher..In murine models, S-TEX are qualified for therapy control and follow-up studies. Despite rapid clearance from the serum, Exo uptake by host cells is most promising for tailored Exo as drug transporter. ..
- Chan C, Munusamy P, Loke S, Koh G, Wong E, Law H, et al. Identification of Novel Breast Cancer Risk Loci. Cancer Res. 2017;77:5428-5437 pubmed publisher..amino acids encoded at these three SNP sites were conserved evolutionarily and associated with decreased protein stability, suggesting a likely impact on protein function...
- Finkenwirth F, Kirsch F, Eitinger T. Complex Stability During the Transport Cycle of a Subclass I ECF Transporter. Biochemistry. 2017;56:4578-4583 pubmed publisher..The data demonstrate that S units of subclass I ECF transporters do not have to dissociate from holotransporter complexes for high-affinity substrate binding, indicating mechanistic differences between the two subclasses...
- Carrington B, Myers W, Horanyi P, Calmiano M, Lawson A. Natural Conformational Sampling of Human TNF? Visualized by Double Electron-Electron Resonance. Biophys J. 2017;113:371-380 pubmed publisher..The new structure offers opportunities to modulate the biological activity of tumor necrosis factor ? through stabilization of the distorted trimer with small molecules. ..
- Abeyrathne P, Grigorieff N. Expression, purification, and contaminant detection for structural studies of Ralstonia metallidurance ClC protein rm1. PLoS ONE. 2017;12:e0180163 pubmed publisher..We were able to obtain properly folded pure ClC-rm1 by adding eGFP to the C-terminus and overexpressing the protein in the ?acrB variant of the JW0451-2 E. coli strain. ..
- Ruan L, Zhou C, Jin E, Kucharavy A, Zhang Y, Wen Z, et al. Cytosolic proteostasis through importing of misfolded proteins into mitochondria. Nature. 2017;543:443-446 pubmed publisher..We term this mitochondria-mediated proteostasis mechanism MAGIC (mitochondria as guardian in cytosol) and provide evidence that it may exist in human cells. ..
- Hu W, Xiang J, Kong P, Liu L, Xie Q, Xiang H. Expression and Characterization of a Single-Chain Variable Fragment against Human LOX-1 in Escherichia coli and Brevibacillus choshinensis. J Microbiol Biotechnol. 2017;27:965-974 pubmed publisher..53E-07 M, 52.5 ± 0.3°C, and 13.54 nm for the scFv expressed by E. coli. This study established an efficient scale-up production methodology for the anti-LOX-1 scFv, which will boost its use in LOX-1-based therapy. ..
- Wang S, Borschel W, Heyman S, Hsu P, Nichols C. Conformational changes at cytoplasmic intersubunit interactions control Kir channel gating. J Biol Chem. 2017;292:10087-10096 pubmed publisher..We conclude that the removal of stabilizing CD-I salt bridges results in a collapsed state of the Kir domain. ..
- Blancas Mejia L, Martin E, Williams A, Wall J, Ramirez Alvarado M. Kinetic stability and sequence/structure studies of urine-derived Bence-Jones proteins from multiple myeloma and light chain amyloidosis patients. Biophys Chem. 2017;230:89-98 pubmed publisher..The kinetic component of protein stability is not a universal feature of BJPs and the hysteresis observed during refolding reactions could be ..