Olga A Vinogradova

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which induces cascades of intracellular signaling events, including protein phosphorylation and cytoskel-etal reorganization (Schwartz et al., 1995; Shattil and Ginsberg, 1997). However, ligand binding to integrins is not simply controlled by ligand availability but also through " inside-out " signaling: cellular stimulation clus-3 Joseph J. Jacobs Center(More)
Activation of the ligand binding function of integrin heterodimers requires transmission of an "inside-out" signal from their small intracellular segments to their large extracellular domains. The structure of the cytoplasmic domain of a prototypic integrin alpha(IIb)beta(3) has been solved by NMR and reveals multiple hydrophobic and electrostatic contacts(More)
Cytoplasmic face-mediated integrin inside-out activation remains a paradigm in transmembrane signal transduction. Emerging evidence suggests that this process involves dissociation of the complex between the integrin cytoplasmic tails; however, a dynamic image of how it occurs on the membrane surface remains elusive. We show here that, whereas(More)
It goes without saying that the cellular plasma membrane effectively creates a barrier between the inside (intracellular area) and outside (extracellular area) of the cell it defi nes. In order for the cell to sense and respond to its environment (including other cells and the supporting structures that comprise the extracellular matrix [ECM]) and for the(More)
Weak protein-protein interactions (PPIs) (K(D) > 10(-6) M) are critical determinants of many biological processes. However, in contrast to a large growing number of well-characterized, strong PPIs, the weak PPIs, especially those with K(D) > 10(-4) M, are poorly explored. Genome wide, there exist few 3D structures of weak PPIs with K(D) > 10(-4) M, and none(More)
Skelemin is a large cytoskeletal protein critical for cell morphology. Previous studies have suggested that its two-tandem immunoglobulin C2-like repeats (SkIgC4 and SkIgC5) are involved in binding to integrin beta3 cytoplasmic tail (CT), providing a mechanism for skelemin to regulate integrin-mediated signaling and cell spreading. Using NMR spectroscopy,(More)
The adenovirus E3-13.7 protein interferes with endosomal protein sorting to down-regulate the epidermal growth factor receptor and related tyrosine kinase receptors. The cytoplasmic C terminus of this protein contains three protein sorting motifs which are related to the function of E3-13.7. In this study, the structure of a 23-residue polypeptide(More)
Translational diffusion coefficients and catalytic activities were measured for the integral membrane protein diacylglycerol kinase (DAGK) in a variety of types of detergent micelles. Despite the structural diversity of the detergents examined, the translational diffusion coefficients observed for DAGK spanned a fairly limited range of values: 2.7 to 4.7(More)
Phosphoantigen-sensitive Vγ9Vδ2 T cells are important responders to infections and malignancy. However, the mechanisms by which phosphoantigens stimulate Vγ9Vδ2 T cells are unclear. Here, we synthesized phosphoantigen prodrugs and used them to demonstrate that intracellular delivery of phosphoantigens is required for their activity. The pivaloyloxymethyl(More)
There is a significant need for new therapeutics to treat infections caused by the biodefense agent Bacillus anthracis. In pursuit of drug discovery against this organism, we have developed novel propargyl-linked inhibitors that target the essential enzyme dihydrofolate reductase (DHFR) from B. anthracis. Previously, we reported an initial series of these(More)