Search results for "protein conformation"
showing 10 items of 515 documents
Role of glycine-82 as a pivot point during the transition from the inactive to the active form of the yeast Ras2 protein
1991
AbstractRas proteins bind either GDP or GTP with high affinity. However, only the GTP-bound form of the yeast Ras2 protein is able to stimulate adenylyl cyclase. To identify amino acid residues that play a role in the conversion from the GDP-bound to the GTP-bound state of Ras proteins, we have searched for single amino acid substitutions that selectively affected the binding of one of the two nucleotides. We have found that the replacement of glycine-82 of the Ras2 protein by serine resulted in an increased rate of dissociation of Gpp(NH)p, a nonhydrolysable analog of GTP, while the GDP dissociation rate was not significantly modified. Glycine-82 resides in a region that is highly conserve…
Central Serotonin2C Receptor: From Physiology to Pathology
2006
Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has…
Apical transport of osteopontin is independent of N-glycosylation and sialylation.
2002
Studies of how epithelial surface polarity into apical and basolateral domains is generated and maintained have proposed that carbohydrate modifications serve as apical targeting signals for proteins by interacting with lectin sorters. However, the experimental evidence in support of N-glycans, O-glycans and sialic acids mediating apical transport is still very controversial. This could be partly due to the fact that in most studies exogenously expressed proteins were analysed. One has, therefore, examined the role of carbohydrate moieties in apical targeting of the endogenous secretory protein osteopontin in MDCK cells. It was found, however, that sorting of osteopontin does not require N-…
The crystal structure of bacteriophage Qβ at 3.5 å resolution
1996
Abstract Background: The capsid protein subunits of small RNA bacteriophages form a T=3 particle upon assembly and RNA encapsidation. Dimers of the capsid protein repress translation of the replicase gene product by binding to the ribosome binding site and this interaction is believed to initiate RNA encapsidation. We have determined the crystal structure of phage Qβ with the aim of clarifying which factors are the most important for particle assembly and RNA interaction in the small phages. Results The crystal structure of bacteriophage Qβ determined at 3.5 a resolution shows that the capsid is stabilized by disulfide bonds on each side of the flexible loops that are situated around the fi…
A topology-constrained distance network algorithm for protein structure determination from NOESY data.
2005
This article formulates the multidi- mensional nuclear Overhauser effect spectroscopy (NOESY) interpretation problem using graph theory and presents a novel, bottom-up, topology-con- strained distance network analysis algorithm for NOESY cross peak interpretation using assigned resonances. AutoStructure is a software suite that implements this topology-constrained distance net- work analysis algorithm and iteratively generates structures using the three-dimensional (3D) protein structure calculation programs XPLOR/CNS or DY- ANA. The minimum input for AutoStructure in- cludes the amino acid sequence, a list of resonance assignments, and lists of 2D, 3D, and/or 4D-NOESY cross peaks. AutoStru…
The silicatein propeptide acts as inhibitor/modulator of self-organization during spicule axial filament formation.
2013
Silicateins are crucial enzymes that are involved in formation of the inorganic biosilica scaffold of the spicular skeleton of siliceous sponges. We show that silicatein acquires its structure-guiding and enzymatically active state by processing of silicatein from pro-silicatein to the mature enzyme. A recombinant propeptide (PROP) of silicatein from the siliceous demosponge Suberites domuncula was prepared, and antibodies were raised against the peptide. In sponge tissue, these antibodies reacted with both surface structures and the central region of the spicules. Using phage display expression, spicule-binding 12-mer peptides were identified that are rich in histidine residues. In the pre…
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 …
Protein aggregation/crystallization and minor structural changes: universal versus specific aspects.
2007
AbstractProtein association covers wide interests in biophysics, protein science, and biotechnologies, and it is often viewed as governed by conformation details. More recently, the existence of a universal physical principle governing aggregation/crystallization processes has been suggested by a series of experiments and shown to be linked to the universal scaling properties of concentration fluctuations occurring in the proximity of a phase transition (spinodal demixing in the specific case). Such properties have provided a quantitative basis for capturing kinetic association data on a universal master curve, ruled by the normalized distance of the state of the system from its instability…
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…
Staphylococcal alpha-toxin: formation of the heptameric pore is partially cooperative and proceeds through multiple intermediate stages.
1997
Staphylococcal alpha-toxin is a 293 residue polypeptide that assembles into pore-forming heptamers, residues 118-140, thereby inserting to form an amphipathic beta-barrel in the lipid bilayer. Fluorometric analyses were here conducted using cysteine-substitution mutants site-specifically-labeled at positions 35 or 130 with the environmentally-sensitive fluorophore acrylodan. In conjunction with functional assays, three conformational states of the heptamer were defined, which may represent transitional configurations of the toxin molecule along its way to membrane insertion and pore formation. The first was the freshly assembled, SDS-sensitive heptamer alpha7*a, where a minor alteration in …