Publications by authors named "Yelena Koldobskaya"

The post-translational modification (PTM) of proteins by O-linked β--acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. Here, we describe etworking of nteractors and ubstrats (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome.

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Structured RNA elements within the internal ribosome entry site (IRES) of hepatitis C virus (HCV) genome hijack host cell machinery for translation initiation through a cap-independent mechanism. Here, using a phage display selection, we obtained two antibody fragments (Fabs), HCV2 and HCV3, against HCV IRES that bind the RNA with dissociation constants of 32 ± 7 nM and 37 ± 8 nM respectively, specifically recognizing the so-called junction IIIabc (JIIIabc). We used these Fabs as crystallization chaperones and determined the high-resolution crystal structures of JIIIabc-HCV2 and -HCV3 complexes at 1.

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Picornaviral IRES elements are essential for initiating the cap-independent viral translation. However, three-dimensional structures of these elements remain elusive. Here, we report a 2.

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Spinach is an in vitro-selected RNA aptamer that binds a GFP-like ligand and activates its green fluorescence. Spinach is thus an RNA analog of GFP and has potentially widespread applications for in vivo labeling and imaging. We used antibody-assisted crystallography to determine the structures of Spinach both with and without bound fluorophore at 2.

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Background: In systemic lupus erythematosus (SLE), antibodies directed at RNA-binding proteins (anti-RBP) are associated with high serum type I interferon (IFN), which plays an important role in SLE pathogenesis. African-Americans (AA) are more likely to develop SLE, and SLE is also more severe in this population. We hypothesized that peripheral blood gene expression patterns would differ between AA and European-American (EA) SLE patients, and between those with anti-RBP antibodies and those who lack these antibodies.

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Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS) of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-α). In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs) for validation.

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All models of the RNA world era invoke the presence of ribozymes that can catalyse RNA polymerization. The class I ligase ribozyme selected in vitro 15 years ago from a pool of random RNA sequences catalyses formation of a 3',5'-phosphodiester linkage analogous to a single step of RNA polymerization. Recently, the three-dimensional structure of the ligase was solved in complex with U1A RNA-binding protein and independently in complex with an antibody fragment.

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RNA crystallization and phasing represent major bottlenecks in RNA structure determination. Seeking to exploit antibody fragments as RNA crystallization chaperones, we have used an arginine-enriched synthetic Fab library displayed on phage to obtain Fabs against the class I ligase ribozyme. We solved the structure of a Fab-ligase complex at 3.

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Primordial organisms of the putative RNA world would have required polymerase ribozymes able to replicate RNA. Known ribozymes with polymerase activity best approximating that needed for RNA replication contain at their catalytic core the class I RNA ligase, an artificial ribozyme with a catalytic rate among the fastest of known ribozymes. Here we present the 3.

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Olefin complexes (silox)(3)M(ole) (silox = (t)Bu(3)SiO; M = Nb (1-ole), Ta (2-ole); ole = C(2)H(4), C(2)H(3)Me, C(2)H(3)Et, C(2)H(3)C(6)H(4)-p-X (X = OMe, H, CF(3)), C(2)H(3)(t)Bu, (c)C(5)H(8), (c)C(6)H(10), (c)C(7)H(10) (norbornene)) rearrange to alkylidene isomers (silox)(3)M(alk) (M = Nb (1=alk), Ta (2=alk); alk = CHMe, CHEt, CH(n)Pr, CHCH(2)C(6)H(4)-p-X (X = OMe, H, CF(3) (Ta only)), CHCH(2)(t)Bu, (c)C(5)H(8), (c)C(6)H(10), (c)C(7)H(10) (norbornylidene)). Kinetics and labeling experiments suggest that the rearrangement proceeds via a delta-abstraction on a silox CH bond by the beta-olefin carbon to give (silox)(2)RM(kappa(2)-O,C-OSi(t)Bu(2)CMe(2)CH(2)) (M = Nb (4-R), Ta (6-R); R = Me, Et, (n)Pr, (n)Bu, CH(2)CH(2)C(6)H(4)-p-X (X = OMe, H, CF(3) (Ta only)), CH(2)CH(2)(t)Bu, (c)C(5)H(9), (c)C(6)H(11), (c)C(7)H(11) (norbornyl)). A subsequent alpha-abstraction by the cylometalated "arm" of the intermediate on an alpha-CH bond of R generates the alkylidene 1=alk or 2=alk.

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