"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.

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

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

Superresolution microscopy reveals distinct localisation of full length IRSp53 and its I-BAR domain protein within filopodia

Published date : 21 Feb 2019

Superresolution microscopy offers the advantage of imaging biological structures within cells at the nano-scale. Here we apply two superresolution microscopy techniques, specifically 3D structured illumination microscopy (3D-SIM) and direct stochastic optical reconstruction microscopy (dSTORM), a type of single molecule localisation microscopy, to localise IRSp53 protein and its I-BAR domain in relation to F-actin within filopodia. IRSp53 generates dynamic (extending and retracting) filopodia 300 nm wide with a distinct gap between IRSp53 and F-actin.

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Journal Paper
journal
Scientific Reports 9, Article no: 2524(2019). doi: 10.1038/s41598-019-38851-w
Impact Factor
4.122

Application Notes on APD Areametric App: Automated area quantification for both Android and iOS

Published date : 08 Feb 2019

Area measurements have a wide range of uses from the monitoring of skin features in healthcare, celestial bodies in astronomy, to determining furniture sizes in everyday indoor uses. Current measurement methods utilize some form of measuring tool and unless performed by skilled and trained professionals, human errors leading to inaccurate measurements can often arise. This is especially so for irregularly shaped objects with complex dimensions.

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Journal Paper
journal
APD Trove 2019, Vol: 2;1, doi: 10.30943/2019/08022019

A Review of Apps for Programming: programming languages and making apps with apps

Published date : 26 Jan 2019

With the latest technologies enabling smartphones to work like mini computers, there are now numerous opportunities to use smartphones for the development of mobile apps. Given the multiple Operating Systems (OS) available, there is a significant demand for apps for the various platforms. To meet this demand, some apps exist to impart the necessary knowledge to make apps, while others make the programming of apps possible on these devices. Surveying both the Google Play and Apple App stores, there are a plethora of such programming apps, classified based on the various languages.

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Journal Paper
journal
Scientific Phone Apps and Mobile Devices (2019) 5:1, doi:10.30943/2019/25012019

Kinetic and thermodynamic effects of phosphorylation on p53 binding to MDM2

Published date : 24 Jan 2019

p53 is frequently mutated in human cancers. Its levels are tightly regulated by the E3 ubiquitin ligase MDM2. The complex between MDM2 and p53 is largely formed by the interaction between the N-terminal domain of MDM2 and the N-terminal transactivation (TA) domain of p53 (residues 15-29). We investigated the kinetic and thermodynamic basis of the MDM2/p53 interaction by using wild-type and mutant variants of the TA domain. We focus on the effects of phosphorylation at positions Thr18 and Ser20 including their substitution with phosphomimetics.

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Journal Paper
journal
Scientific Reports 9, Article no: 693 (2019). doi: 10.1038/s41598-018-36589-5
Impact Factor
4.122

Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations

Published date : 24 Jan 2019

Dengue is a mosquito-borne virus with dire health and economic impacts. Dengue is responsible for an estimated 390 million infections per year, with dengue 2 (DENV2) being the most virulent strain among the four serotypes. Interestingly, it is also in strains of this serotype that temperature-dependent large-scale morphological changes, termed “breathing,” have been observed. Although the structure of these morphologies has been solved to 3.5-Å resolution, the dynamics of the viral envelope are unknown.

type
Journal Paper
journal
Structure, 27, Pg 1-13, 2019, doi: 10.1016/j.str.2018.12.006
Impact Factor
4.907

Organic cation transporter 3 (Oct3) is a distinct catecholamines clearance route in adipocytes mediating the beiging of white adipose tissue

Published date : 17 Jan 2019

Beiging of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of metabolic diseases through norepinephrine (NE)-mediated signaling pathways. Although previous studies report NE clearance mechanisms via SLC6A2 on sympathetic neurons or proinflammatory macrophages in adipose tissues (ATs), the low catecholamine clearance capacity of SLC6A2 may limit the cleaning efficiency.

type
Journal Paper
journal
PLOS Biology, January 17 2019, doi: 10.1371/journal.pbio.2006571
Impact Factor
9.163