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81.
82.
Willy Carrasquel-Ursulaez Gustavo F. Contreras Romina V. Sepúlveda Daniel Aguayo Fernando González-Nilo Carlos González Ramón Latorre 《The Journal of general physiology》2015,145(1):61-74
Large-conductance Ca2+- and voltage-activated K+ channel (BK) open probability is enhanced by depolarization, increasing Ca2+ concentration, or both. These stimuli activate modular voltage and Ca2+ sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca2+, profoundly hinders channel opening while showing only minor effects on the voltage sensor active–resting equilibrium. Interpretation of these results using an allosteric model suggests that the F380A mutation greatly increases the free energy difference between open and closed states and uncouples Ca2+ binding from voltage sensor activation and voltage sensor activation from channel opening. However, the presence of a bulky and more hydrophobic amino acid in the F380 position (F380W) increases the intrinsic open–closed equilibrium, weakening the coupling between both sensors with the pore domain. Based on these functional experiments and molecular dynamics simulations, we propose that F380 interacts with another S6 hydrophobic residue (L377) in contiguous subunits. This pair forms a hydrophobic ring important in determining the open–closed equilibrium and, like an integration node, participates in the communication between sensors and between the sensors and pore. Moreover, because of its effects on open probabilities, the F380A mutant can be used for detailed voltage sensor experiments in the presence of permeant cations. 相似文献
83.
Wei‐Hsiang Lin Mark J. Rocco Amelia Bertozzi‐Villa Edo Kussell 《Evolution; international journal of organic evolution》2015,69(6):1448-1460
Populations can adapt to changing environments by using allelic diversity, yet whether diversity is recently derived or ancestral is often debated. Although evolution could productively use both types of diversity in a changing environment, their relative frequency has not been quantified. We address this question experimentally using budding yeast strains that harbor a tandem repeat containing URA3 gene, which we expose to cyclical selection and counterselection. We characterize and quantify the dynamics of frameshift events in the URA3 gene in eight populations over 12 cycles of selection and find that ancestral alleles account for 10–20% of all adaptive events. Using a general model of fluctuating selection, we determine how these results depend on mutation rates, population sizes, and fluctuation timescales. We quantify the contribution of derived alleles to the adaptation process using the de novo mutation rate along the population's ancestral lineage, a novel measure that is applicable in a wide range of settings. We find that the adaptive dynamics undergoes a sharp transition from selection on ancestral alleles to selection on derived alleles as fluctuation timescales increase. Our results demonstrate that fluctuations can select between different modes of adaptation over evolutionary timescales. 相似文献
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87.
Giulia Di Rocco Gianantonio Battistuzzi Carlo Augusto Bortolotti Marco Borsari Erika Ferrari Stefano Monari Marco Sola 《Journal of biological inorganic chemistry》2011,16(3):461-471
The 16-kDa diheme cytochrome c from the bacterium Shewanella baltica OS155 (Sb-DHC) was cloned and expressed in Escherichia coli and investigated through UV–vis, magnetic circular dichroism, and 1H NMR spectroscopies and protein voltammetry. The model structure was obtained by means of comparative modeling using the
X-ray structure of Rhodobacter sphaeroides diheme cytochrome c (Rs-DHC) (with a 37% pairwise sequence identity) as a template. Sb-DHC folds into two distinct domains, each containing one
heme center with a bis-His axial ligation. Both secondary and tertiary structures of the N-terminal domain resemble those
of class I cytochrome c, displaying three α-helices and a compact overall folding. The C-terminal domain is less helical than the corresponding domain
of Rs-DHC. The two heme groups are bridged by Tyr26 in correspondence with the shortest edge-to-edge distance, a feature which
would facilitate fast internal electron transfer. The electronic properties of the two prosthetic centers are equivalent and
sensitive to two acid–base equilibria with pK
a values of approximately 2.4 and 5, likely corresponding to protonation and detachment of the axial His ligands from the heme
iron and a pH-linked conformational change of the protein, respectively. Reduction potentials of −0.144 and −0.257 V (vs.
the standard hydrogen electrode), were determined for the C- and N-terminal heme groups, respectively. An approach based on
the extended Debye–Hückel equation was applied for the first time to a two-centered metalloprotein and was found to reproduce
successfully the ionic strength dependence of E°′. 相似文献
88.
The genome sequencing of Buchnera aphidicola BCc from the aphid Cinara cedri, which is the smallest known Buchnera genome, revealed that this bacterium had lost its symbiotic role, as it was not able to synthesize tryptophan and riboflavin. Moreover, the biosynthesis of tryptophan is shared with the endosymbiont Serratia symbiotica SCc, which coexists with B. aphidicola in this aphid. The whole-genome sequencing of S. symbiotica SCc reveals an endosymbiont in a stage of genome reduction that is closer to an obligate endosymbiont, such as B. aphidicola from Acyrthosiphon pisum, than to another S. symbiotica, which is a facultative endosymbiont in this aphid, and presents much less gene decay. The comparison between both S. symbiotica enables us to propose an evolutionary scenario of the transition from facultative to obligate endosymbiont. Metabolic inferences of B. aphidicola BCc and S. symbiotica SCc reveal that most of the functions carried out by B. aphidicola in A. pisum are now either conserved in B. aphidicola BCc or taken over by S. symbiotica. In addition, there are several cases of metabolic complementation giving functional stability to the whole consortium and evolutionary preservation of the actors involved. 相似文献
89.
Huber D Rajagopalan N Preissler S Rocco MA Merz F Kramer G Bukau B 《Molecular cell》2011,41(3):343-353
In Escherichia coli, translocation of exported proteins across the cytoplasmic membrane is dependent on the motor protein SecA and typically begins only after synthesis of the substrate has already been completed (i.e., posttranslationally). Thus, it has generally been assumed that the translocation machinery also recognizes its protein substrates posttranslationally. Here we report a specific interaction between SecA and the ribosome at a site near the polypeptide exit channel. This interaction is mediated by conserved motifs in SecA and ribosomal protein L23, and partial disruption of this interaction in?vivo by introducing mutations into the genes encoding SecA or L23 affects the efficiency of translocation by the posttranslational pathway. Based on these findings, we propose that SecA could interact with its nascent substrates during translation in order to efficiently channel them into the "posttranslational" translocation pathway. 相似文献
90.
Gentile A Toietta G Pazzano V Tsiopoulos VD Giglio AF Crea F Pompilio G Capogrossi MC Di Rocco G 《Molecular biology of the cell》2011,22(5):581-592
Recent studies have underscored a role for the epicardium as a source of multipotent cells. Here, we investigate the myogenic potential of adult human epicardium-derived cells (EPDCs) and analyze their ability to undergo skeletal myogenesis when cultured with differentiating primary myoblasts. Results are compared to those obtained with mesenchymal stromal cells (MSCs) and with endothelial cells, another mesodermal derivative. We demonstrate that EPDCs spontaneously fuse with pre-existing myotubes with an efficiency that is significantly higher than that of other cells. Although at a low frequency, endothelial cells may also contribute to myotube formation. In all cases analyzed, after entering the myotube, nonmuscle nuclei are reprogrammed to express muscle-specific genes. The fusion competence of nonmyogenic cells in vitro parallels their ability to reconstitute dystrophin expression in mdx mice. We additionally show that vascular cell adhesion molecule 1 (VCAM1) expression levels of nonmuscle cells are modulated by soluble factors secreted by skeletal myoblasts and that VCAM1 function is required for fusion to occur. Finally, treatment with interleukin (IL)-4 or IL-13, two cytokines released by differentiating myotubes, increases VCAM1 expression and enhances the rate of fusion of EPDCs and MSCs, but not that of endothelial cells. 相似文献