Zinc and RNA Binding Is Linked to the Conformational Flexibility of ZRANB2: A CCCC-Type Zinc Finger Protein.

Ran-binding domain-containing protein 2 (ZRANB2) is a zinc finger (ZF) protein that plays a key role in alternative splicing. ZRANB2 is composed of two ZF domains that contain four invariant cysteine residues per domain. ZRANB2 binds RNA targets that contain AGGUAA sequence motifs.

Structural Dynamics of the Dengue Virus Non-structural 5 (NS5) Interactions with Promoter Stem Loop A (SLA).

The dengue virus (DENV) NS5 protein plays a central role in dengue viral RNA synthesis which makes it an attractive target for antiviral drug development. DENV NS5 is known to interact with the stem-loop A (SLA) promoter at the 5'-untranslated region (5'-UTR) of the viral genome as a molecular recognition signature for the initiation of negative strand synthesis at the 3' end of the viral genome. However, the conformational dynamics involved in these interactions are yet to be fully elucidated.

Characterization of cross-reactive, non-neutralizing monoclonal antibodies against a pandemic GII.4 norovirus variant.

Unlabelled: Antibodies are thought to play a major role in protection against human norovirus infection. Mouse humoral responses closely mimic those of humans; thus, mouse models are used to characterize norovirus epitopes on the major viral capsid protein, VP1. We have developed a panel of mouse monoclonal antibodies (mAbs) produced against the last pandemic variant to emerge, Sydney 2012.

VICR: A novel software for unbiased video and image analysis in scientific research.

In scientific research, objectivity and unbiased data analysis is crucial for the validity and reproducibility of outcomes. This is particularly important for studies involving video or image categorization. A common approach of decreasing the bias is delegating data analysis to researchers unfamiliar with the experimental settings.

Integration of Hydrogen-Deuterium Exchange Mass Spectrometry with Molecular Dynamics Simulations and Ensemble Reweighting Enables High Resolution Protein-Ligand Modeling.

Hydrogen-Deuterium exchange mass spectrometry's (HDX-MS) utility in identifying and characterizing protein-small molecule interaction sites has been established. The regions that are seen to be protected from exchange upon ligand binding indicate regions that may be interacting with the ligand, giving a qualitative understanding of the ligand binding pocket. However, quantitatively deriving an accurate high-resolution structure of the protein-ligand complex from the HDX-MS data remains a challenge, often limiting its use in applications such as small molecule drug design.

VICR: A Novel Software for Unbiased Video and Image Analysis in Scientific Research.

In scientific research, objectivity and unbiased data analysis is crucial for the validity and reproducibility of outcomes. This is particularly important for studies involving video or image categorization. A common approach of decreasing the bias is delegating data analysis to researchers unfamiliar with the experimental settings.

Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling.

Interleukin-1 (IL-1)-family cytokines are potent modulators of inflammation, coordinating a vast array of immunological responses across innate and adaptive immune systems. Dysregulated IL-1-family cytokine signaling, however, is involved in a multitude of adverse health effects, such as chronic inflammatory conditions, autoimmune diseases, and cancer. Within the IL-1 family of cytokines, six-IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ-require the IL-1 receptor accessory protein (IL-1RAcP) as their shared co-receptor.

Development and characterization of nanobodies that specifically target the oncogenic Phosphatase of Regenerating Liver-3 (PRL-3) and impact its interaction with a known binding partner, CNNM3.

Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis. The mechanisms that drive PRL-3's oncogenic functions are not well understood, partly due to a lack of research tools available to study this protein. We have begun to address these issues by developing alpaca-derived single domain antibodies, or nanobodies, targeting PRL-3 with a KD of 30-300 nM and no activity towards highly homologous family members PRL-1 and PRL-2.

Long-range allostery mediates the regulation of plasminogen activator inhibitor-1 by cell adhesion factor vitronectin.

The serpin plasminogen activator inhibitor 1 (PAI-1) spontaneously undergoes a massive structural change from a metastable and active conformation, with a solvent-accessible reactive center loop (RCL), to a stable, inactive, or latent conformation, with the RCL inserted into the central β-sheet. Physiologically, conversion to the latent state is regulated by the binding of vitronectin, which hinders the latency transition rate approximately twofold. The molecular mechanisms leading to this rate change are unclear.

Molecular Basis of Selective Cytokine Signaling Inhibition by Antibodies Targeting a Shared Receptor.

Interleukin-1 (IL-1) family cytokines are potent mediators of inflammation, acting to coordinate local and systemic immune responses to a wide range of stimuli. Aberrant signaling by IL-1 family cytokine members, however, is linked to myriad inflammatory syndromes, autoimmune conditions and cancers. As such, blocking the inflammatory signals inherent to IL-1 family signaling is an established and expanding therapeutic strategy.

Modeling the native ensemble of PhuS using enhanced sampling MD and HDX-ensemble reweighting.

The cytoplasmic heme binding protein from Pseudomonas aeruginosa, PhuS, plays two essential roles in regulating heme uptake and iron homeostasis. First, PhuS shuttles exogenous heme to heme oxygenase (HemO) for degradation and iron release. Second, PhuS binds DNA and modulates the transcription of the prrF/H small RNAs (sRNAs) involved in the iron-sparing response.

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate.

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e.

Interpreting Hydrogen-Deuterium Exchange Experiments with Molecular Simulations: Tutorials and Applications of the HDXer Ensemble Reweighting Software [Article v1.0].

Hydrogen-deuterium exchange (HDX) is a comprehensive yet detailed probe of protein structure and dynamics and, coupled to mass spectrometry, has become a powerful tool for investigating an increasingly large array of systems. Computer simulations are often used to help rationalize experimental observations of exchange, but interpretations have frequently been limited to simple, subjective correlations between microscopic dynamical fluctuations and the observed macroscopic exchange behavior. With this in mind, we previously developed the HDX ensemble reweighting approach and associated software, HDXer, to aid the objective interpretation of HDX data using molecular simulations.

Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation.

Fucosylation is important for the function of many proteins with biotechnical and medical applications. Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins. Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.