ATP-independent assembly machinery of bacterial outer membranes: BAM complex structure and function set the stage for next-generation therapeutics.

Diderm bacteria employ β-barrel outer membrane proteins (OMPs) as their first line of communication with their environment. These OMPs are assembled efficiently in the asymmetric outer membrane by the β-Barrel Assembly Machinery (BAM). The multi-subunit BAM complex comprises the transmembrane OMP BamA as its functional subunit, with associated lipoproteins (e.

Empowering canonical biochemicals with cross-linked novelty: Recursions in applications of protein cross-links.

Diversity in the biochemical workhorses of the cell-that is, proteins-is achieved by the innumerable permutations offered primarily by the 20 canonical L-amino acids prevalent in all biological systems. Yet, proteins are known to additionally undergo unusual modifications for specialized functions. Of the various post-translational modifications known to occur in proteins, the recently identified non-disulfide cross-links are unique, residue-specific covalent modifications that confer additional structural stability and unique functional characteristics to these biomolecules.

Photoradical-Mediated Catalyst-Independent Protein Cross-Link with Unusual Fluorescence Properties.

Photo-actively modified natural amino acids have served as lucrative probes for precise mapping of the dynamics, interaction networks, and turnover of cytosolic proteins both in vivo and ex vivo. In our attempts to extend the utility of photoreactive reporters to map the molecular characteristics of vital membrane proteins, we carried out site-selective incorporation of 7-fluoro-indole in the human mitochondrial outer membrane protein VDAC2 (voltage-dependent anion channel isoform 2), with the aim of generating Trp-Phe/Tyr cross-links. Prolonged irradiation at 282 nm provided us with a surprisingly unusual fluorophore that displayed sizably red-shifted excitation (λ =280 nm→360 nm) and emission (λ =330 nm→430 nm) spectra that was reversible with organic solvents.

Occurrence and distribution of heavy metals in water and soil sediments of Vellore District, Tamil Nadu, India.

The occurrence of heavy metals (HMs) in water and soil sediments represents a serious environmental concern. This study revealed the presence and distribution of HMs in water and soil sediments of various places in Vellore District, Tamil Nadu, India. Twenty-one sites were selected along the study area, and inductively coupled plasma-optical emission spectrometry (ICP-OES) was used to analyze the concentration of the heavy metals.

Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation.

The human mitochondrial outer membrane is biophysically unique as it is the only membrane possessing transmembrane β-barrel proteins (mitochondrial outer membrane proteins, mOMPs) in the cell. The most vital of the three mOMPs is the core protein of the translocase of the outer mitochondrial membrane (TOM) complex. Identified first as MOM38 in Neurospora in 1990, the structure of Tom40, the core 19-stranded β-barrel translocation channel, was solved in 2017, after nearly three decades.

Engineering a Hyperstable Outer Membrane Protein Ail Using Thermodynamic Design.

Development of viable therapeutics to effectively combat tier I pneumopathogens such as requires a thorough understanding of proteins vital for pathogenicity. The host invasion protein Ail, although indispensable for pathogenesis, has evaded detailed characterization, as it is an outer membrane protein with intrinsically low stability and high aggregation propensity. Here, we identify molecular elements of the metastable Ail structure that considerably alter protein-lipid and intraprotein thermodynamics.

Frictional Forces Produced by Three Different Ligation Methods in Two Different Types of Brackets in 0.016 Nickel-Titanium Wire: An Study.

Introduction: The aim of this study was to compare the frictional forces produced by three types of ligatures (conventional elastic ligatures, unconventional elastic ligatures, and tooth-colored ligature wire) on ceramic bracket and stainless steel brackets with 0.016 nickeltitanium (NiTi) archwire in the dry state.

Materials And Methods: Twenty each stainless steel brackets and ceramic brackets (0.

Hormetic effect of low doses of rapamycin triggers anti-aging cascades in WRL-68 cells by modulating an mTOR-mitochondria cross-talk.

Background: Rapamycin is hormetic in nature-it demonstrates contrasting effects at high and low doses. It is toxic at moderate/high doses, while it can restrain aging and extend lifespan at low doses. However, it is not fully understood how rapamycin governs cellular aging.

Cellular Interactome of Mitochondrial Voltage-Dependent Anion Channels: Oligomerization and Channel (Mis)Regulation.

Voltage-dependent anion channels (VDACs) of the outer mitochondrial membrane are known conventionally as metabolite flux proteins. However, research findings in the past decade have revealed the multifaceted regulatory roles of VDACs, from governing cellular physiology and mitochondria-mediated apoptosis to directly regulating debilitating cancers and neurodegenerative diseases. VDACs achieve these diverse functions by establishing isoform-dependent stereospecific interactomes in the cell with the cytosolic constituents and endoplasmic reticulum complexes, and the machinery of the mitochondrial compartments.

Evaluation of Horizontal Distance between WALA-FA Point in Angle's Class I, Class II, and Class III Malocclusion.

Introduction: The objective of the study was to measure the horizontal distance between the FA-WALA (Facial Axis Point-William Andrews and Larry Andrews) of posterior teeth in Angle's Class I, Class II, and Class III malocclusions and to assess the depth of the Curve of Spee, to find the correlation between intercanine FA and intercanine WALA and its significance.

Material And Methods: Sixty pretreatment mandibular casts of patients with an age range of 18-35 years were included. A sample size of 20 was evaluated in Angle's Class I, Class II, and Class III, respectively.

Interplay of protein primary sequence, lipid membrane, and chaperone in β-barrel assembly.

The outer membrane of a Gram-negative bacterium is a crucial barrier between the external environment and its internal physiology. This barrier is bridged selectively by β-barrel outer membrane proteins (OMPs). The in vivo folding and biogenesis of OMPs necessitates the assistance of the outer membrane chaperone BamA.

Evolutionary selection of a 19-stranded mitochondrial β-barrel scaffold bears structural and functional significance.

Transmembrane β-barrels of eukaryotic outer mitochondrial membranes (OMMs) are major channels of communication between the cytosol and mitochondria and are indispensable for cellular homeostasis. A structurally intriguing exception to all known transmembrane β-barrels is the unique odd-stranded, 19-stranded, structures found solely in the OMM. The molecular origins of this 19-stranded structure and its associated functional significance are unclear.

Hexavalent chromium-induced autophagic death of WRL-68 cells is mitigated by aqueous extract of L. seeds.

In this study, we assessed the potential of aqueous extract (CSE) of L. (cumin) seeds in protecting WRL-68 cells from hexavalent chromium [Cr(VI)]-induced oxidative injury. Cells exposed to Cr(VI) (10 μM CrO) for 24 h demonstrated a twofold increase in ROS, which, in turn, led to extensive oxidative stress, consequently causing colossal decline in cell viability (by 58.

Chelating modified cellulose bearing pendant heterocyclic moiety for effective removal of heavy metals.

Cellulose bearing pendant Schiff base with heterocyclic chelating groups (CMC-Bz) was synthesized, which were fully characterized using various instrumental techniques such as solid state carbon-13 nuclear magnetic resonance (C-NMR), Fourier transform infrared (FTIR), scanning electron microscope (SEM) and energy dispersive X-ray analysis (EDX) spectra. The adsorption of toxic metals onto cellulosic material was tested in a batch mode operation. The adsorption functional factors such as pH, adsorbent dose, metal ion concentration, equilibrium time and temperature were experimentally optimized for the maximum removal of Cu(II) and Pb(II) ions.

Single-residue physicochemical characteristics kinetically partition membrane protein self-assembly and aggregation.

Ninety-five percent of all transmembrane proteins exist in kinetically trapped aggregation-prone states that have been directly linked to neurodegenerative diseases. Interestingly, the primary sequence almost invariably avoids off-pathway aggregate formation, by folding reliably into its native, thermodynamically stabilized structure. However, with the rising incidence of protein aggregation diseases, it is now important to understand the underlying mechanism(s) of membrane protein aggregation.

Molecular Switch between Structural Compaction and Thermodynamic Stability by the Xxx-Pro Interface in Transmembrane β-Barrels.

Transmembrane β-barrel scaffolds found in outer membrane proteins are formed and stabilized by a defined pattern of interstrand intraprotein H-bonds, in hydrophobic lipid bilayers. Introducing the conformationally constrained proline in β-barrels can cause significant destabilization of these structural regions that require H-bonding, with proline additionally acting as a secondary structure breaker. Membrane protein β-barrels are therefore expected to show poor tolerance to the presence of a transmembrane proline.

Reversible folding energetics of Yersinia Ail barrel reveals a hyperfluorescent intermediate.

Deducing the molecular details of membrane protein folding has lately become an important area of research in biology. Using Ail, an outer membrane protein (OMP) from Yersina pestis as our model, we explore details of β-barrel folding, stability, and unfolding. Ail displays a simple transmembrane β-barrel topology.

Hydrophobic Characteristic Is Energetically Preferred for Cysteine in a Model Membrane Protein.

The naturally occurring amino acid cysteine has often been implicated with a crucial role in maintaining protein structure and stability. An intriguing duality in the intrinsic hydrophobicity of the cysteine side chain is that it exhibits both polar as well as hydrophobic characteristics. Here, we have utilized a cysteine-scanning mutational strategy on the transmembrane β-barrel PagP to examine the membrane depth-dependent energetic contribution of the free cysteine side chain (thiolate) versus the parent residue at an experimental pH of 9.

Helix-strand interaction regulates stability and aggregation of the human mitochondrial membrane protein channel VDAC3.

Voltage-dependent anion channels (VDACs) are β-sheet-rich transmembrane β-barrels that are vital for metabolite transport across the mitochondrial membrane. Under cellular stress, human VDACs hetero-oligomerize and coaggregate with proteins that can form amyloidogenic and neurodegenerative deposits, implicating a role for VDACs in proteotoxicity. However, whether VDACs possess intrinsic interaction sites that can lead to protein aggregation is not known.

Hydrophobic Mismatch Modulates Stability and Plasticity of Human Mitochondrial VDAC2.

The human mitochondrial outer membrane protein voltage-dependent anion channel isoform 2 (hVDAC2) is a β-barrel metabolite flux channel that is indispensable for cell survival. It is well established that physical forces imposed on a transmembrane protein by its surrounding lipid environment decide protein structure and stability. Yet, how the mitochondrial membrane and protein-lipid interplay together regulate hVDAC2 stability is unknown.

Aromatic interactions in β-hairpin scaffold stability: A historical perspective.

Non-covalent interactions between naturally occurring aromatic residues have been widely exploited as scaffold stabilizing agents in de novo designed peptides and in Nature - inspired structures. Our understanding of the factors driving aromatic interactions and their observed interaction geometries have advanced remarkably with improvements in conventional structural studies, availability of novel molecular methods and in silico studies, which have together provided atomistic information on aromatic interactions and interaction strengths. This review attempts to recapitulate the early advances in our understanding of aromatic interactions as stabilizing agents of peptide β-hairpins.

Salvaging the Thermodynamic Destabilization of Interface Histidine in Transmembrane β-Barrels.

The ability of histidine to participate in a wide range of stabilizing polar interactions preferentially populates this residue in functionally important sites of proteins. Histidine possesses an amphiphilic and electrostatic nature that is essential for amino acids residing at membrane interfaces. However, the frequency of occurrence of histidine at membrane interfaces, particularly transmembrane β-barrels, is lower than those of other aromatic residues.