Search results for "MUTATION"
showing 10 items of 2830 documents
Efficient DNA Packaging of Bacteriophage PRD1 Requires the Unique Vertex Protein P6
2007
ABSTRACT The assembly of bacteriophage PRD1 proceeds via formation of empty procapsids containing an internal lipid membrane, into which the linear double-stranded DNA genome is subsequently packaged. The packaging ATPase P9 and other putative packaging proteins have been shown to be located at a unique vertex of the PRD1 capsid. Here, we describe the isolation and characterization of a suppressor-sensitive PRD1 mutant deficient in the unique vertex protein P6. Protein P6 was found to be an essential part of the PRD1 packaging machinery; its absence leads to greatly reduced packaging efficiency. Lack of P6 was not found to affect particle assembly, because in the P6-deficient mutant infecti…
Effect of T-R conformational change on sickle-cell hemoglobin interactions and aggregation
2004
We compare the role of a conformational switch and that of a point mutation in the thermodynamic stability of a protein solution and in the consequent propensity toward aggregation. We study sickle-cell hemoglobin (HbS), the beta6 Glu-Val point mutant of adult human hemoglobin (HbA), in its R (CO-liganded) conformation, and compare its aggregation properties to those of both HbS and HbA in their T (unliganded) conformation. Static and dynamic light scattering measurements performed for various hemoglobin concentrations showed critical divergences with mean field exponents as temperature was increased. This allowed determining spinodal data points T(S)(c) by extrapolation. These points were …
Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.
2021
The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…
The Molecular Basis of X-Linked Spondyloepiphyseal Dysplasia Tarda
2001
The X-linked form of spondyloepiphyseal dysplasia tarda (SEDL), a radiologically distinct skeletal dysplasia affecting the vertebrae and epiphyses, is caused by mutations in the SEDL gene. To characterize the molecular basis for SEDL, we have identified the spectrum of SEDL mutations in 30 of 36 unrelated cases of X-linked SEDL ascertained from different ethnic populations. Twenty-one different disease-associated mutations now have been identified throughout the SEDL gene. These include nonsense mutations in exons 4 and 5, missense mutations in exons 4 and 6, small (2–7 bp) and large (>1 kb) deletions, insertions, and putative splicing errors, with one splicing error due to a complex deleti…
Elimination of a bacterial pore-forming toxin by sequential endocytosis and exocytosis
2008
Staphylococcus aureus alpha-toxin is the archetype of bacterial pore forming toxins and a key virulence factor secreted by the majority of clinical isolates of S. aureus. Toxin monomers bind to target cells and oligomerize to form small beta-barrel pores in the plasma membrane. Many nucleated cells are able to repair a limited number of lesions by unknown, calcium-independent mechanisms. Here we show that cells can internalize alpha-toxin, that uptake is essential for cellular survival, and that pore-complexes are not proteolytically degraded, but returned to the extracellular milieu in the context of exosome-like structures, which we term toxosomes.
Lipid and phase specificity of α-toxin from S. aureus
2013
AbstractThe pore forming toxin Hla (α-toxin) from Staphylococcus aureus is an important pathogenic factor of the bacterium S. aureus and also a model system for the process of membrane-induced protein oligomerisation and pore formation. It has been shown that binding to lipid membranes at neutral or basic pH requires the presence of a phosphocholine-headgroup. Thus, sphingomyelin and phosphatidylcholine may serve as interaction partners in cellular membranes. Based on earlier studies it has been suggested that rafts of sphingomyelin are particularly efficient in toxin binding. In this study we compared the oligomerisation of Hla on liposomes of various lipid compositions in order to identif…
Substitution systems and nonextensive statistics
2015
Abstract Substitution systems evolve in time by generating sequences of symbols from a finite alphabet: At a certain iteration step, the existing symbols are systematically replaced by blocks of N k symbols also within the alphabet (with N k , a natural number, being the length of the k th block of the substitution). The dynamics of these systems leads naturally to fractals and self-similarity. By using B -calculus (Garcia-Morales, 2012) universal maps for deterministic substitution systems both of constant and non-constant length, are formulated in 1D. It is then shown how these systems can be put in direct correspondence with Tsallis entropy. A ‘Second Law of Thermodynamics’ is also prove…
A parallel and sensitive software tool for methylation analysis on multicore platforms.
2015
Abstract Motivation: DNA methylation analysis suffers from very long processing time, as the advent of Next-Generation Sequencers has shifted the bottleneck of genomic studies from the sequencers that obtain the DNA samples to the software that performs the analysis of these samples. The existing software for methylation analysis does not seem to scale efficiently neither with the size of the dataset nor with the length of the reads to be analyzed. As it is expected that the sequencers will provide longer and longer reads in the near future, efficient and scalable methylation software should be developed. Results: We present a new software tool, called HPG-Methyl, which efficiently maps bis…
RNA viruses as complex adaptive systems
2004
RNA viruses have high mutation rates and so their populations exist as dynamic and complex mutant distributions. It has been consistently observed that when challenged with a new environment, viral populations adapt following hyperbolic-like kinetics: adaptation is initially very rapid, but then slows down as fitness reaches an asymptotic value. These adaptive dynamics have been explained in terms of populations moving towards the top of peaks on rugged fitness landscapes. Fitness fluctuations of varying magnitude are observed during adaptation. Often the presence of fluctuations in the evolution of physical systems indicates some form of self-organization, or where many components of the s…
On the empirical spectral distribution for certain models related to sample covariance matrices with different correlations
2021
Given [Formula: see text], we study two classes of large random matrices of the form [Formula: see text] where for every [Formula: see text], [Formula: see text] are iid copies of a random variable [Formula: see text], [Formula: see text], [Formula: see text] are two (not necessarily independent) sets of independent random vectors having different covariance matrices and generating well concentrated bilinear forms. We consider two main asymptotic regimes as [Formula: see text]: a standard one, where [Formula: see text], and a slightly modified one, where [Formula: see text] and [Formula: see text] while [Formula: see text] for some [Formula: see text]. Assuming that vectors [Formula: see t…