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831.
Peptide aptamers define distinct EB1- and EB3-binding motifs and interfere with microtubule dynamics
Karolina Le?niewska Emma Warbrick Hiroyuki Ohkura 《Molecular biology of the cell》2014,25(7):1025-1036
EB1 is a conserved protein that plays a central role in regulating microtubule dynamics and organization. It binds directly to microtubule plus ends and recruits other plus end–localizing proteins. Most EB1-binding proteins contain a Ser–any residue–Ile-Pro (SxIP) motif. Here we describe the isolation of peptide aptamers with optimized versions of this motif by screening for interaction with the Drosophila EB1 protein. The use of small peptide aptamers to competitively inhibit protein interaction and function is becoming increasingly recognized as a powerful technique. We show that SxIP aptamers can bind microtubule plus ends in cells and functionally act to displace interacting proteins by competitive binding. Their expression in developing flies can interfere with microtubules, altering their dynamics. We also identify aptamers binding to human EB1 and EB3, which have sequence requirements similar to but distinct from each other and from Drosophila EB1. This suggests that EB1 paralogues within one species may interact with overlapping but distinct sets of proteins in cells. 相似文献
832.
Endonuclease V (EndoV) is a metal-dependent DNA repair enzyme involved in removal of deaminated bases (e.g., deoxyuridine,
deoxyinosine, and deoxyxanthosine), with pairing specificities different from the original bases. Homologs of EndoV are present
in all major phyla from bacteria to humans and their function is quite well analyzed. EndoV has been combined with DNA ligase
to develop an enzymatic method for mutation scanning and has been engineered to obtain variants with different substrate specificities
that serve as improved tools in mutation recognition and cancer mutation scanning. However, little is known about the structure
and mechanism of substrate DNA binding by EndoV. Here, we present the results of a bioinformatic analysis and a structural
model of EndoV from Escherichia coli in complex with DNA. The structure was obtained by a combination of fold-recognition, comparative modeling, de novo modeling
and docking methods. The modeled structure provides a convenient tool to study protein sequence-structure-function relationships
in EndoV and to engineer its further variants. 相似文献
833.
Robert E. Jefferson Duyoung Min Karolina Corin Jing Yang Wang James U. Bowie 《Journal of molecular biology》2018,430(4):424-437
Protein folding is a fundamental life process with many implications throughout biology and medicine. Consequently, there have been enormous efforts to understand how proteins fold. Almost all of this effort has focused on water-soluble proteins, however, leaving membrane proteins largely wandering in the wilderness. The neglect has occurred not because membrane proteins are unimportant but rather because they present many theoretical and technical complications. Indeed, quantitative membrane protein folding studies are generally restricted to a handful of well-behaved proteins. Single-molecule methods may greatly alter this picture, however, because the ability to work at or near infinite dilution removes aggregation problems, one of the main technical challenges of membrane protein folding studies. 相似文献
834.
835.
837.
Michal Mikula Karolina Hanusek Agnieszka Paziewska Artur Dzwonek Tymon Rubel Karol Bomsztyk Jerzy Ostrowski 《BMC molecular biology》2010,11(1):4
Background
Aberrant activation of protein kinases is one of the essential oncogenic driving forces inherent to the process of tumorigenesis. The protein kinase CK2 plays an important role in diverse biological processes, including cell growth and proliferation as well as in the governing and transduction of prosurvival signals. Increased expression of CK2 is a hallmark of some cancers, hence its antiapoptotic properties may be relevant to cancer onset. Thus, the designing and synthesis of the CK2 inhibitors has become an important pursuit in the search for cancer therapies. 相似文献838.
Justyna Czech-Kowalska Edyta Czekuc-Kryskiewicz Pawel Pludowski Katarzyna Zaniuk Maciej Jaworski Anna ?uba Karolina Grzybowska Krystyna Pi?at Anna Dobrzanska 《PloS one》2016,11(11)
BackgroundMetabolic bone disease of prematurity still occurs in preterm infants, although a significant improvement in neonatal care has been observed in recent decades. Dual-energy X-ray absorptiometry (DXA) is the precise technique for assessing bone mineral content (BMC) in preterm infants, but is not widely available.AimTo investigate the clinical and biochemical parameters, including bone metabolism markers as potential predictors of BMC, in preterm infants up to 3 months corrected age (CA).ResultsThe appropriate quality DXA scans were available for 160 infants (87%) examined at term and for 130 (71%) tested at 3 mo CA. Higher iPTH level was the only independent predictor of lower BMC at term, whereas lower BMC at 3 mo CA was associated both with lower urinary phosphate excretion and higher serum osteocalcin level. ROC analysis showed that iPTH >43.6 pg/mL provided 40% sensitivity and 88% specificity in identification of preterm infants with lower BMC at term. In turn, urinary phosphate excretion (TRP>97% or UP/Cr ≤0.74 mg/mg) and serum osteocalcin >172 ng/mL provided 40% sensitivity and 93% specificity in identification of infants with decreased BMC at 3 mo CA.ConclusionSerum iPTH might to be a simple predictor of reduced BMC in preterm infants at term age, but urinary phosphate excretion and serum osteocalcin might predict reduced BMC at 3 mo CA. These results represent a promising diagnostic tool based on simple, widely available biochemical measurements for bone mass assessment in preterm infants. 相似文献
839.
Jingjing Zhou Marine Lnon Jean-Luc Ravanat Nadia Touati Christophe Velours Karolina Podskoczyj Grazyna Leszczynska Marc Fontecave Frdric Barras Batrice Golinelli-Pimpaneau 《Nucleic acids research》2021,49(7):3997
Sulfuration of uridine 34 in the anticodon of tRNAs is conserved in the three domains of life, guaranteeing fidelity of protein translation. In eubacteria, it is catalyzed by MnmA-type enzymes, which were previously concluded not to depend on an iron–sulfur [Fe–S] cluster. However, we report here spectroscopic and iron/sulfur analysis, as well as in vitro catalytic assays and site-directed mutagenesis studies unambiguously showing that MnmA from Escherichia coli can bind a [4Fe–4S] cluster, which is essential for sulfuration of U34-tRNA. We propose that the cluster serves to bind and activate hydrosulfide for nucleophilic attack on the adenylated nucleoside. Intriguingly, we found that E. coli cells retain s2U34 biosynthesis in the ΔiscUA ΔsufABCDSE strain, lacking functional ISC and SUF [Fe–S] cluster assembly machineries, thus suggesting an original and yet undescribed way of maturation of MnmA. Moreover, we report genetic analysis showing the importance of MnmA for sustaining oxidative stress. 相似文献
840.