Sam Porter Millar
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ABSTRACT:
SUBMITTER: Millar J
PROVIDER: S-EPMC1463940 | biostudies-literature | 2006 May
REPOSITORIES: biostudies-literature
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Project description:Arap3 is a phosphatidylinositol 3 kinase effector protein that plays a role as GTPase activator (GAP) for Arf6 and RhoA. Arap3 contains a sterile alpha motif (Sam) domain that has high sequence homology with the Sam domain of the EphA2-receptor (EphA2-Sam). Both Arap3-Sam and EphA2-Sam are able to associate with the Sam domain of the lipid phosphatase Ship2 (Ship2-Sam). Recently, we reported a novel interaction between the first Sam domain of Odin (Odin-Sam1), a protein belonging to the ANKS (ANKyrin repeat and Sam domain containing) family, and EphA2-Sam. In our latest work, we applied NMR spectroscopy, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) to characterize the association between Arap3-Sam and Odin-Sam1. We show that these two Sam domains interact with low micromolar affinity. Moreover, by means of molecular docking techniques, supported by NMR data, we demonstrate that Odin-Sam1 and Arap3-Sam might bind with a topology that is common to several Sam-Sam complexes. The revealed structural details form the basis for the design of potential peptide antagonists that could be used as chemical tools to investigate functional aspects related to heterotypic Arap3-Sam associations.
| S-EPMC3631714 | biostudies-literature
Project description: Not available
| S-EPMC4847381 | biostudies-literature
Project description:The relationship between luminous intensity and the maximum frequency of flicker that can be detected defines the limits of the temporal-resolving ability of the human visual system, and characterizing it has important theoretical and practical applications; particularly for determining the optimal refresh rate for visual displays that would avoid the visibility of flicker and other temporal artifacts. Previous research has shown that this relationship is best described by the Ferry-Porter law, which states that critical flicker fusion (CFF) increases as a linear function of log retinal illuminance. The existing experimental data showed that this law holds for a wide range of stimuli and up to 10,000 Trolands; however, beyond this, it was not clear if the CFF continued to increase linearly or if the function saturated. Our aim was to extend the experimental data available to higher light intensities than previously reported in the literature. For this, we measured the peripheral CFF at a range of illuminances over six orders of magnitude. Our results showed that for up to 104 Trolands, the data conformed to the Ferry-Porter law with a similar slope, as previously established for this eccentricity; however, at higher intensities, the CFF function flattens and saturates at ~90 Hz for a target size of 5.7 degrees, and at ~100 Hz for a target of 10 degrees of angular size. These experimental results could prove valuable for the design of brighter visual displays and illumination sources that are temporally modulated.
| S-EPMC10057432 | biostudies-literature
Project description:Tandem SAM-II/SAM-V riboswitch belongs to a class of riboswitches found in the marine bacterium 'Candidatus Pelagibacter ubique'. Previous studies have demonstrated that these riboswitches have the potential for digital modulation of gene expression at both the transcriptional and translational levels. In this study, we investigate the conformational changes in the tandem SAM-II/SAM-V riboswitch binding to S-adenosylmethionine (SAM) using selective 2'-hydroxyl acylation analyzed by the primer extension (SHAPE) assay, small-angle X-ray scattering (SAXS), and oligos depressing probing. Our findings reveal that the linker between SAM-II/SAM-V aptamers blocks the SAM response of the SAM-II domain. This result proposes a new mechanism for gene expression regulation, where the ligand-binding functions of tandem riboswitches can be selectively masked or released through a linker.
| S-EPMC11508383 | biostudies-literature
Project description:BackgroundSterile alpha motif (Sam) domains are small protein modules that can be involved in homotypic or heterotypic associations and exhibit different functions. Previous studies have demonstrated that the Sam domain of the lipid phosphatase Ship2 can hetero-dimerize with the Sam domain of the PI3K effector protein Arap3.ResultsHere, we determine the NMR solution structure of Arap3-Sam and implement a multidisciplinary approach consisting of NMR spectroscopy, ITC (Isothermal Titration Calorimetry), mutagenesis and molecular modeling studies to analyze the interaction between Ship2-Sam and Arap3-Sam. This work reveals that Arap3-Sam may associate with Ship2-Sam by adopting a binding mode common to other Sam domains. This binding mode is identical to what we have very recently observed for the association between Ship2-Sam and the Sam domain from the Ephrin A2 receptor.ConclusionOur studies further clarify the structural features that are relevant for Sam-Sam interactions involving Ship2 and give additional hints that could be used for the identification of new molecules able to selectively inhibit Sam-Sam associations.
| S-EPMC2755476 | biostudies-literature
Project description:The first chloride transporter identified in the superfamily of ClC chloride channels was from Escherichia coli (EClC) (Accardi, A., and Miller, C. (2004) Nature 427, 803-807). Pathways, energetics, and mechanism of proton and chloride translocation and their coupling are up to now unclear. To bridge the hydrophobic gap of proton transport, we modeled four stable buried waters into both subunits of the WT EClC structure. Together they form a "water wire" connecting Glu-203 with the chloride at the central site, which in turn connects to Glu-148, the hypothetical proton exit site. Assuming the transient production of hydrochloride in the central chloride binding site of EClC, the water wire could establish a transmembrane proton transport pathway starting from Glu-203 all the way downstream onto Glu-148. We demonstrated by electrostatic and quantum chemical computations that protonation of the central chloride is energetically feasible. We characterized all chloride occupancies and protonation states possibly relevant for the proton-chloride transport cycle in EClC and constructed a working model. Accordingly, EClC evolves through states involving up to two excess protons and between one and three chlorides, which was required to fulfill the experimentally observed 2:1 stoichiometry. We show that the Y445F and E203H mutants of EClC can operate similarly, thus explaining why they exhibit almost WT activity levels. The proposed mechanism of coupled chloride-proton transport in EClC is consistent with available experimental data and allows predictions on the importance of specific amino acids, which may be probed by mutation experiments.
| S-EPMC3024792 | biostudies-literature