Allostery in Its Many Disguises: From Theory to Applications

Published date : 01 Apr 2019

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood.

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Journal Paper
journal
Structure 27, 2019 Jan 17. pii: S0969-2126(19)30003-6. doi: 10.1016/j.str.2019.01.003
Impact Factor
4.907

Structure mapping of dengue and Zika viruses reveals functional long-range interactions

Published date : 29 Mar 2019

Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates.

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Journal Paper
journal
Nature Communications, 2019 Mar 29;10(1):1408. doi: 10.1038/s41467-019-09391-8
Impact Factor
12.353

Proteomic and bioinformatic analyses for the identification of proteins with low allergenic potential for hazard assessment

Published date : 23 Mar 2019

Use of botanicals and natural substances in consumer products has increased in recent years. Such extracts can contain protein that may theoretically represent a potential risk of IgE-mediated allergy. No method has yet been generally accepted or validated for assessment of the allergenic potential of proteins. For development of suitable methods datasets of allergenic and non-allergenic (or low allergenic) proteins are required that can serve, respectively, as positive and negative controls. However, data are unavailable on proteins that lack or have low allergenic potential.

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Journal Paper
journal
Toxicological Sciences, 2019 Mar 23. pii: kfz078. doi: 10.1093/toxsci/kfz078.
Impact Factor
4.081

Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism

Published date : 22 Mar 2019

Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid biosynthesis and adipogenesis by controlling the expression of several enzymes required for cholesterol, fatty acid, triacylglycerol and phospholipid synthesis. In vertebrates, SREBP activation is mainly controlled by a complex and well-characterized feedback mechanism mediated by cholesterol, a crucial bio-product of the SREBP-activated mevalonate pathway.

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Journal Paper
journal
Nature Communications, 2019 Mar 22;10(1):1326. doi: 10.1038/s41467-019-09152-7
Impact Factor
12.353

Inhibition of the NLRP3 inflammasome activation by cell-permeable stapled peptides

Published date : 20 Mar 2019

Interleukin-1β (IL-1β) is a major cytokine that initiates and enhances inflammatory responses. Excessive IL-1β production is a characteristic of most chronic inflammatory diseases, including atherosclerosis, type 2 diabetes, and obesity, which affect a large proportion of the global population. The production of bioactive IL-1β is mediated by a caspase-1-activating complex known as an ‘inflammasome’. The NLRP3 inflammasome has been associated with several human inflammatory and autoimmune diseases and represents a potential therapeutic target for disrupting IL-1β production.

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Journal Paper
journal
Scientific Reports 9, Article no. 4913 (2019), doi: 10.1038/s41598-019-41211-3
Impact Factor
4.122

"Inhibiting S100B(ββ) for Activating Wild-Type p53: Design of Stapled Peptides"

Published date : 14 Mar 2019

S100B(ββ) is a member of the S100B protein family and is distributed in a cell-specific manner. Its levels are elevated in several cancers such as malignant melanoma and correlate directly with poor prognosis in patients. S100B(ββ) directly interacts with the tumor suppressor p53, inhibiting tetramerization and protein kinase C-dependent phosphorylation, consequently decreasing p53 DNA binding and transcriptional activity, and preventing apoptosis. Thus, S100B(ββ) is being pursued as a target for therapeutic inhibition.

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Journal Paper
journal
ACS Omega 2019, 5, Pg 5335-5344, doi: 10.1021/acsomega.9b00097

Phylogenetic Clustering by Linear Integer Programming (PhyCLIP)

Published date : 11 Mar 2019

Sub-species nomenclature systems of pathogens are increasingly based on sequence data. The use of phylogenetics to identify and differentiate between clusters of genetically similar pathogens is particularly prevalent in virology from the nomenclature of human papillomaviruses to highly pathogenic avian influenza (HPAI) H5Nx viruses. These nomenclature systems rely on absolute genetic distance thresholds to define the maximum genetic divergence tolerated between viruses designated as closely related.

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Journal Paper
journal
Molecular Biology and Evolution, 2019 Mar 11. pii: msz053. doi: 10.1093/molbev/msz053
Impact Factor
10.217

An inter-subunit protein-peptide interface that stabilizes the specific activity and oligomerization of the AAA+ chaperone Reptin

Published date : 09 Mar 2019

Reptin is a member of the AAA+ superfamily whose members can exist in equilibrium between monomeric apo forms and ligand bound hexamers. Inter-subunit protein-protein interfaces that stabilize Reptin in its oligomeric state are not well-defined. A self-peptide binding assay identified a protein-peptide interface mapping to an inter-subunit “rim” of the hexamer bridged by Tyrosine-340. A Y340A mutation reduced ADP-dependent oligomer formation using a gel filtration assay, suggesting that Y340 forms a dominant oligomer stabilizing side chain.

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Journal Paper
journal
Journal of Proteomics, Vol. 199, 2019, Pg 89-101 doi:10.1016/j.jprot.2019.02.012
Impact Factor
3.722

Insights into water accessible pathways and the inactivation mechanism of proton translocation by the membrane-embedded domain of V-type ATPases

Published date : 01 Mar 2019

V-type ATPases are multi-protein complexes, which acidify cellular compartments in eukaryotes. They pump protons against an ion gradient, driven by a mechano-chemical framework that exploits ATP hydrolysis as an energy source. This process drives the rotation of the so-called c-ring, a membrane embedded complex in the Vo-domain of the V-type ATPase, resulting in translocation of protons across the membrane. One way in which the enzyme is regulated is by disassembly and reassembly of the V1-domain with the Vo-domain, which inactivates and reactivates the enzyme, respectively.

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Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1861, Issue 5, 1 May 2019, Pg 1004-1010, doi: 10.1016/j.bbamem.2019.02.010
Impact Factor
3.438

The disordered plant dehydrin Lti30 protects the membrane during water-related stress by cross-linking lipids

Published date : 28 Feb 2019

Dehydrins are intrinsically disordered proteins, generally expressed in plants as a response to embryogenesis and water-related stress. Their suggested functions are in membrane stabilization and cell protection. All dehydrins contain at least one copy of the highly conserved K-segment, proposed to be a membrane binding motif. The dehydrin Lti30 (Arabidopsis thaliana) is upregulated during cold and drought stress conditions and comprises six K-segments, each with two adjacent histidines. Lti30 interacts with the membrane electrostatically via pH dependent protonation of the histidines.

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Journal Paper
journal
Journal of Biological Chemistry, 28 Feb 2019, doi: 10.1074/jbc.RA118.007163
Impact Factor
4.011