Search results for "Interaction domains"
showing 10 items of 46 documents
Serviceability and Ultimate Safety Checks of SegmentalConcrete Bridges through N-M and M-V Interaction Domains
2015
In current engineering practice, safety checks on serviceability and determinations of ultimate limit states of segmental bridges built by cantilevering are generally performed, either considering separately the contributions of axial force N, bending moment M, and shear force V, or considering the interaction effects through approximate expressions supplied by building codes. During construction stages and service life, the interaction between internal forces can be of fundamental importance in establishing the actual degree of structural safety and, for this reason, a different philosophy for performing checks in segmental bridges is proposed in this paper, plotting N-M and M-V interactio…
Interaction between Longitudinal Shear and Transverse Bending in Prestressed Concrete Box Girders
2017
In box girder bridges, the quantity and distribution of reinforcement to be put in concrete elements of sections can be evaluated only by considering the deformation of the cross section in addition to the longitudinal analysis of the static scheme, establishing the entire state of stress of box sections. This leads to a need to evaluate the interaction between internal forces obtained by the global analysis and the ones obtained by the local analysis of the cross sections. The frame effect implies the elastic deformation of slabs and webs, whereas eccentrically applied loads lead to cross-section distortion with the loss of the box shape. Hence, the reinforcement is strongly influenced by …
MMGBSA As a Tool To Understand the Binding Affinities of Filamin–Peptide Interactions
2013
Filamins (FLN) are large dimeric proteins that cross-link actin and work as important scaffolds in human cells. FLNs consist of an N-terminal actin-binding domain followed by 24 immunoglobulin-like domains (FLN1-24). FLN domains are divided into four subgroups based on their amino acid sequences. One of these subgroups, including domains 4, 9, 12, 17, 19, 21, and 23, shares a similar ligand-binding site between the β strands C and D. Several proteins, such as integrins β2 and β7, glycoprotein Ibα (GPIbα), and migfilin, have been shown to bind to this site. Here, we computationally estimated the binding free energies of filamin A (FLNa) subunits with bound peptides using the molecular mechan…
Tracking Ca
2019
We characterize thus-far elusive domain rearrangements of a calcium-transporting ATPase in the native membrane.
Mating systems and protein–protein interactions determine evolutionary rates of primate sperm proteins
2013
To assess the relative impact of functional constraint and post-mating sexual selection on sequence evolution of reproductive proteins, we examined 169 primate sperm proteins. In order to recognize potential genome-wide trends, we additionally analysed a sample of altogether 318 non-reproductive (brain and postsynaptic) proteins. Based on cDNAs of eight primate species (Anthropoidea), we observed that pre-mating sperm proteins engaged in sperm composition and assembly show significantly lower incidence of site-specific positive selection and overall lower non-synonymous to synonymous substitution rates ( d N / d S ) across sites as compared with post-mating sperm proteins involved in capac…
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurologi…
2019
Abstract KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel α-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the …
Synaptosomes: new vesicles for neuronal mitochondrial transplantation
2021
Abstract Background Mitochondrial dysfunction is a critical factor in the onset and progression of neurodegenerative diseases. Recently, mitochondrial transplantation has been advised as an innovative and attractive strategy to transfer and replace damaged mitochondria. Here we propose, for the first time, to use rat brain extracted synaptosomes, a subcellular fraction of isolated synaptic terminal that contains mitochondria, as mitochondrial delivery systems. Results Synaptosome preparation was validated by the presence of Synaptophysin and PSD95. Synaptosomes were characterized in terms of dimension, zeta potential, polydispersity index and number of particles/ml. Nile Red or CTX-FITCH la…
A protein quality control pathway regulated by linear ubiquitination.
2019
Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC, is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence doma…
Fluidizing the Membrane by a Local Anesthetic: Phenylethanol Affects Membrane Protein Oligomerization
2010
The exact mechanism of action of anesthetics is still an open question. While some observations suggest specific anesthetic-protein interactions, nonspecific perturbation of the lipid bilayer has also been suggested. Perturbations of bilayer properties could subsequently affect the structure and function of membrane proteins. Addition of the local anesthetic phenylethanol (PEtOH) to model membranes and intact Escherichia coli cells not only affected membrane fluidity but also severely altered the defined helix-helix interaction within the membrane. This experimental observation suggests that certain anesthetics modulate membrane physical properties and thereby indirectly affect transmembran…
Metallothionein Gene Family in the Sea Urchin Paracentrotus lividus: Gene Structure, Differential Expression and Phylogenetic Analysis
2017
Metallothioneins (MT) are small and cysteine-rich proteins that bind metal ions such as zinc, copper, cadmium, and nickel. In order to shed some light on MT gene structure and evolution, we cloned seven Paracentrotus lividus MT genes, comparing them to Echinodermata and Chordata genes. Moreover, we performed a phylogenetic analysis of 32 MTs from different classes of echinoderms and 13 MTs from the most ancient chordates, highlighting the relationships between them. Since MTs have multiple roles in the cells, we performed RT-qPCR and in situ hybridization experiments to understand better MT functions in sea urchin embryos. Results showed that the expression of MTs is regulated throughout de…