Biomolecules

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Open AccessArticle

An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation

by Emmanuel Oppong, Gunter Stier, Miriam Gaal, Rebecca Seeger, Melanie Stoeck, Marc-André Delsuc, Andrew C. B. Cato and Bruno Kieffer

Biomolecules 2017, 7(2), 44; https://doi.org/10.3390/biom7020044 - 19 Jun 2017

Cited by 4 | Viewed by 6480

Abstract

The human androgen receptor (AR) is a ligand inducible transcription factor that harbors an amino terminal domain (AR-NTD) with a ligand-independent activation function. AR-NTD is intrinsically disordered and displays aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence. The length of [...] Read more.

The human androgen receptor (AR) is a ligand inducible transcription factor that harbors an amino terminal domain (AR-NTD) with a ligand-independent activation function. AR-NTD is intrinsically disordered and displays aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence. The length of the polyQ sequence as well as its adjacent sequence motifs modulate this aggregation property. AR-NTD also contains a conserved KELCKAVSVSM sequence motif that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions. As peptide sequences with intrinsic oligomerization properties are reported to have an impact on the aggregation of polyQ tracts, we determined the effect of the KELCKAVSVSM on the polyQ stretch in the context of the AR-NTD using atomic force microscopy (AFM). Here, we present evidence for a crosstalk between the amyloidogenic properties of the KELCKAVSVSM motif and the polyQ stretch at the AR-NTD. Full article

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4360 KiB

Open AccessArticle

Sequence Identification, Recombinant Production, and Analysis of the Self-Assembly of Egg Stalk Silk Proteins from Lacewing Chrysoperla carnea

by Martin Neuenfeldt and Thomas Scheibel

Biomolecules 2017, 7(2), 43; https://doi.org/10.3390/biom7020043 - 13 Jun 2017

Cited by 7 | Viewed by 5200

Abstract

Egg stalk silks of the common green lacewing Chrysoperla carnea likely comprise at least three different silk proteins. Based on the natural spinning process, it was hypothesized that these proteins self-assemble without shear stress, as adult lacewings do not use a spinneret. To [...] Read more.

Egg stalk silks of the common green lacewing Chrysoperla carnea likely comprise at least three different silk proteins. Based on the natural spinning process, it was hypothesized that these proteins self-assemble without shear stress, as adult lacewings do not use a spinneret. To examine this, the first sequence identification and determination of the gene expression profile of several silk proteins and various transcript variants thereof was conducted, and then the three major proteins were recombinantly produced in Escherichia coli encoded by their native complementary DNA (cDNA) sequences. Circular dichroism measurements indicated that the silk proteins in aqueous solutions had a mainly intrinsically disordered structure. The largest silk protein, which we named ChryC1, exhibited a lower critical solution temperature (LCST) behavior and self-assembled into fibers or film morphologies, depending on the conditions used. The second silk protein, ChryC2, self-assembled into nanofibrils and subsequently formed hydrogels. Circular dichroism and Fourier transform infrared spectroscopy confirmed conformational changes of both proteins into beta sheet rich structures upon assembly. ChryC3 did not self-assemble into any morphology under the tested conditions. Thereby, through this work, it could be shown that recombinant lacewing silk proteins can be produced and further used for studying the fiber formation of lacewing egg stalks. Full article

(This article belongs to the Special Issue Functional Amyloids)

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215 KiB

Open AccessReview

Vitamin B₁₂ and Semen Quality

by Saleem Ali Banihani

Biomolecules 2017, 7(2), 42; https://doi.org/10.3390/biom7020042 - 9 Jun 2017

Cited by 48 | Viewed by 14459

Abstract

Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm [...] Read more.

Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm physiology. We searched the Web of Science, PubMed, and Scopus databases for only English language articles or abstracts from September 1961 to March 2017 (inclusive) using the key words “vitamin B12” and “cobalamin” versus “sperm”. Certain relevant references were included to support the empirical as well as the mechanistic discussions. In conclusion, the mainstream published work demonstrates the positive effects of vitamin B12 on semen quality: first, by increasing sperm count, and by enhancing sperm motility and reducing sperm DNA damage, though there are a few in vivo system studies that have deliberated some adverse effects. The beneficial effects of vitamin B12 on semen quality may be due to increased functionality of reproductive organs, decreased homocysteine toxicity, reduced amounts of generated nitric oxide, decreased levels of oxidative damage to sperm, reduced amount of energy produced by spermatozoa, decreased inflammation-induced semen impairment, and control of nuclear factor-κB activation. However, additional research, mainly clinical, is still needed to confirm these positive effects. Full article

930 KiB

Open AccessReview

Bifunctional Enzyme JMJD6 Contributes to Multiple Disease Pathogenesis: New Twist on the Old Story

by Shiva Shankar Vangimalla, Murali Ganesan, Kusum K. Kharbanda and Natalia A. Osna

Biomolecules 2017, 7(2), 41; https://doi.org/10.3390/biom7020041 - 1 Jun 2017

Cited by 27 | Viewed by 6117

Abstract

Jumonji domain-containing protein 6 (JMJD6) is a non-heme Fe(II) 2-oxoglutarate (2OG)-dependent oxygenase with arginine demethylase and lysyl hydroxylase activities. Its initial discovery as a dispensable phosphatidylserine receptor (PSR) in the cell membrane of macrophages for phagocytosis was squashed by newer studies which revealed [...] Read more.

Jumonji domain-containing protein 6 (JMJD6) is a non-heme Fe(II) 2-oxoglutarate (2OG)-dependent oxygenase with arginine demethylase and lysyl hydroxylase activities. Its initial discovery as a dispensable phosphatidylserine receptor (PSR) in the cell membrane of macrophages for phagocytosis was squashed by newer studies which revealed its nuclear localization and bifunctional enzymatic activity. Though its interaction with several nuclear and cytoplasmic target proteins has been demonstrated, the exact mechanisms and clinical significance of these various biologic interplays are not yet well established. Recent investigations have shed the light on the multiple pathways by which JMJD6 can regulate cell proliferation and cause tumorigenesis. Clinically, JMJD6 has been associated with more aggressive and metastatic disease, poorer prognosis, and lower overall survival rates—particularly in lung colon and oral cancers. JMJD6 is a novel biomarker for predicting future disease outcomes and is a target for new therapeutic treatments in future studies. Aberrant expression and dysregulation of JMJD6 are implicated in various other processes such as impaired T-cell proliferation and maturation, inoculation, and virulence of foot-and-mouth disease virus (FMDV), and impaired methylation of innate immunity factor. This article reviews the association of JMJD6 with various pathological processes—particularly, its role in tumorigenesis and virological interactions. Full article

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Open AccessReview

Meristem Plant Cells as a Sustainable Source of Redox Actives for Skin Rejuvenation

by Liudmila G. Korkina, Wolfgang Mayer and Chiara De Luca

Biomolecules 2017, 7(2), 40; https://doi.org/10.3390/biom7020040 - 12 May 2017

Cited by 20 | Viewed by 9479

Abstract

Recently, aggressive advertisement claimed a “magic role” for plant stem cells in human skin rejuvenation. This review aims to shed light on the scientific background suggesting feasibility of using plant cells as a basis of anti-age cosmetics. When meristem cell cultures obtained from [...] Read more.

Recently, aggressive advertisement claimed a “magic role” for plant stem cells in human skin rejuvenation. This review aims to shed light on the scientific background suggesting feasibility of using plant cells as a basis of anti-age cosmetics. When meristem cell cultures obtained from medicinal plants are exposed to appropriate elicitors/stressors (ultraviolet, ultrasound ultraviolet (UV), ultrasonic waves, microbial/insect metabolites, heavy metals, organic toxins, nutrient deprivation, etc.), a protective/adaptive response initiates the biosynthesis of secondary metabolites. Highly bioavailable and biocompatible to human cells, low-molecular weight plant secondary metabolites share structural/functional similarities with human non-protein regulatory hormones, neurotransmitters, pigments, polyamines, amino-/fatty acids. Their redox-regulated biosynthesis triggers in turn plant cell antioxidant and detoxification molecular mechanisms resembling human cell pathways. Easily isolated in relatively large quantities from contaminant-free cell cultures, plant metabolites target skin ageing mechanisms, above all redox imbalance. Perfect modulators of cutaneous oxidative state via direct/indirect antioxidant action, free radical scavenging, UV protection, and transition-metal chelation, they are ideal candidates to restore photochemical/redox/immune/metabolic barriers, gradually deteriorating in the ageing skin. The industrial production of plant meristem cell metabolites is toxicologically and ecologically sustainable for fully “biological” anti-age cosmetics. Full article

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Open AccessArticle

TrmL and TusA Are Necessary for rpoS and MiaA Is Required for hfq Expression in Escherichia coli

by Joseph I. Aubee, Morenike Olu and Karl M. Thompson

Biomolecules 2017, 7(2), 39; https://doi.org/10.3390/biom7020039 - 4 May 2017

Cited by 14 | Viewed by 6810

Abstract

Previous work demonstrated that efficient RNA Polymerase sigma S-subunit (RpoS) translation requires the N6-isopentenyladenosine i6A37 transfer RNA (tRNA) modification for UUX-Leu decoding. Here we investigate the effect of two additional tRNA modification systems on RpoS translation; the analysis was also extended to another [...] Read more.

Previous work demonstrated that efficient RNA Polymerase sigma S-subunit (RpoS) translation requires the N6-isopentenyladenosine i6A37 transfer RNA (tRNA) modification for UUX-Leu decoding. Here we investigate the effect of two additional tRNA modification systems on RpoS translation; the analysis was also extended to another High UUX-leucine codon (HULC) protein, Host Factor for phage Qβ (Hfq). One tRNA modification, the addition of the 2’-O-methylcytidine/uridine 34 (C/U34m) tRNA modification by tRNA (cytidine/uridine-2’O)-ribose methyltransferase L (TrmL), requires the presence of the N⁶-isopentenyladenosine 37 (i⁶A37) and therefore it seemed possible that the defect in RpoS translation in the absence of i⁶A37 prenyl transferase (MiaA) was in fact due to the inability to add the C/U34m modification to UUX-Leu tRNAs. The second modification, addition of 2-thiouridine (s²U), part of (mnm⁵s²U34), is dependent on tRNA 2-thiouridine synthesizing protein A (TusA), previously shown to affect RpoS levels. We compared expression of P_BAD-rpoS990-lacZ translational fusions carrying wild-type UUX leucine codons with derivatives in which UUX codons were changed to CUX codons, in the presence and absence of TrmL or TusA. The absence of these proteins, and therefore presumably the modifications they catalyze, both abolished P_BAD-rpoS990-lacZ translation activity. UUX-Leu to CUX-Leu codon mutations in rpoS suppressed the trmL requirement for P_BAD-rpoS990-lacZ expression. Thus, it is likely that the C/U34m and s²U34 tRNA modifications are necessary for full rpoS translation. We also measured P_BAD-hfq306-lacZ translational fusion activity in the absence of C/U34m (trmL) or i⁶A37 (miaA). The absence of i⁶A37 resulted in decreased P_BAD-hfq306-lacZ expression, consistent with a role for i⁶A37 tRNA modification for hfq translation. Full article

(This article belongs to the Collection RNA Modifications)

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2756 KiB

Open AccessReview

Diversity of Amyloid Motifs in NLR Signaling in Fungi

by Antoine Loquet and Sven J. Saupe

Biomolecules 2017, 7(2), 38; https://doi.org/10.3390/biom7020038 - 13 Apr 2017

Cited by 24 | Viewed by 6332

Abstract

Amyloid folds not only represent the underlying cause of a large class of human diseases but also display a variety of functional roles both in prokaryote and eukaryote organisms. Among these roles is a recently-described activity in signal transduction cascades functioning in host [...] Read more.

Amyloid folds not only represent the underlying cause of a large class of human diseases but also display a variety of functional roles both in prokaryote and eukaryote organisms. Among these roles is a recently-described activity in signal transduction cascades functioning in host defense and programmed cell death and involving Nod-like receptors (NLRs). In different fungal species, prion amyloid folds convey activation signals from a receptor protein to an effector domain by an amyloid templating and propagation mechanism. The discovery of these amyloid signaling motifs derives from the study of [Het-s], a fungal prion of the species Podospora anserina. These signaling pathways are typically composed of two basic components encoded by adjacent genes, the NLR receptor bearing an amyloid motif at the N-terminal end and a cell death execution protein with a HeLo pore-forming domain bearing a C-terminal amyloid motif. Activation of the NLR receptor allows for amyloid folding of the N-terminal amyloid motifs which then template trans-conformation of the homologous motif in the cell death execution protein. A variety of such motifs, which differ by their sequence signature, have been described in fungi. Among them, the PP-motif bears resemblance with the RHIM amyloid motif involved in the necroptosis pathway in mammals suggesting an evolutionary conservation of amyloid signaling from fungi to mammals. Full article

(This article belongs to the Special Issue Functional Amyloids)

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Open AccessArticle

Amyloid Fibrils from Hemoglobin

by Nadishka Jayawardena, Manmeet Kaur, Smitha Nair, Jenny Malmstrom, David Goldstone, Leonardo Negron, Juliet A. Gerrard and Laura J. Domigan

Biomolecules 2017, 7(2), 37; https://doi.org/10.3390/biom7020037 - 11 Apr 2017

Cited by 27 | Viewed by 9637

Abstract

Amyloid fibrils are a class of insoluble protein nanofibers that are formed via the self-assembly of a wide range of peptides and proteins. They are increasingly exploited for a broad range of applications in bionanotechnology, such as biosensing and drug delivery, as nanowires, [...] Read more.

Amyloid fibrils are a class of insoluble protein nanofibers that are formed via the self-assembly of a wide range of peptides and proteins. They are increasingly exploited for a broad range of applications in bionanotechnology, such as biosensing and drug delivery, as nanowires, hydrogels, and thin films. Amyloid fibrils have been prepared from many proteins, but there has been no definitive characterization of amyloid fibrils from hemoglobin to date. Here, nanofiber formation was carried out under denaturing conditions using solutions of apo-hemoglobin extracted from bovine waste blood. A characteristic amyloid fibril morphology was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM), with mean fibril dimensions of approximately 5 nm diameter and up to several microns in length. The thioflavin T assay confirmed the presence of β-sheet structures in apo-hemoglobin fibrils, and X-ray fiber diffraction showed the characteristic amyloid cross-β quaternary structure. Apo-hemoglobin nanofibers demonstrated high stability over a range of temperatures (−20 to 80 °C) and pHs (2–10), and were stable in the presence of organic solvents and trypsin, confirming their potential as nanomaterials with versatile applications. This study conclusively demonstrates the formation of amyloid fibrils from hemoglobin for the first time, and also introduces a cost-effective method for amyloid fibril manufacture using meat industry by-products. Full article

(This article belongs to the Special Issue Functional Amyloids)

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2333 KiB

Open AccessArticle

QueF-Like, a Non-Homologous Archaeosine Synthase from the Crenarchaeota

by Adriana Bon Ramos, Lide Bao, Ben Turner, Valérie De Crécy-Lagard and Dirk Iwata-Reuyl

Biomolecules 2017, 7(2), 36; https://doi.org/10.3390/biom7020036 - 6 Apr 2017

Cited by 10 | Viewed by 5914

Abstract

Archaeosine (G⁺) is a structurally complex modified nucleoside ubiquitous to the Archaea, where it is found in the D-loop of virtually all archaeal transfer RNA (tRNA). Its unique structure, which includes a formamidine group that carries a formal positive charge, and [...] Read more.

Archaeosine (G⁺) is a structurally complex modified nucleoside ubiquitous to the Archaea, where it is found in the D-loop of virtually all archaeal transfer RNA (tRNA). Its unique structure, which includes a formamidine group that carries a formal positive charge, and location in the tRNA, led to the proposal that it serves a key role in stabilizing tRNA structure. Although G⁺ is limited to the Archaea, it is structurally related to the bacterial modified nucleoside queuosine, and the two share homologous enzymes for the early steps of their biosynthesis. In the Euryarchaeota, the last step of the archaeosine biosynthetic pathway involves the amidation of a nitrile group on an archaeosine precursor to give formamidine, a reaction catalyzed by the enzyme Archaeosine Synthase (ArcS). Most Crenarchaeota lack ArcS, but possess two proteins that inversely distribute with ArcS and each other, and are implicated in G⁺ biosynthesis. Here, we describe biochemical studies of one of these, the protein QueF-like (QueF-L) from Pyrobaculum calidifontis, that demonstrate the catalytic activity of QueF-L, establish where in the pathway QueF-L acts, and identify the source of ammonia in the reaction. Full article

(This article belongs to the Collection RNA Modifications)

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6523 KiB

Open AccessReview

tRNA Modifications: Impact on Structure and Thermal Adaptation

by Christian Lorenz, Christina E. Lünse and Mario Mörl

Biomolecules 2017, 7(2), 35; https://doi.org/10.3390/biom7020035 - 4 Apr 2017

Cited by 257 | Viewed by 28928

Abstract

Transfer RNAs (tRNAs) are central players in translation, functioning as adapter molecules between the informational level of nucleic acids and the functional level of proteins. They show a highly conserved secondary and tertiary structure and the highest density of post-transcriptional modifications among all [...] Read more.

Transfer RNAs (tRNAs) are central players in translation, functioning as adapter molecules between the informational level of nucleic acids and the functional level of proteins. They show a highly conserved secondary and tertiary structure and the highest density of post-transcriptional modifications among all RNAs. These modifications concentrate in two hotspots—the anticodon loop and the tRNA core region, where the D- and T-loop interact with each other, stabilizing the overall structure of the molecule. These modifications can cause large rearrangements as well as local fine-tuning in the 3D structure of a tRNA. The highly conserved tRNA shape is crucial for the interaction with a variety of proteins and other RNA molecules, but also needs a certain flexibility for a correct interplay. In this context, it was shown that tRNA modifications are important for temperature adaptation in thermophilic as well as psychrophilic organisms, as they modulate rigidity and flexibility of the transcripts, respectively. Here, we give an overview on the impact of modifications on tRNA structure and their importance in thermal adaptation. Full article

(This article belongs to the Collection RNA Modifications)

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Open AccessReview

The Process and Regulatory Components of Inflammation in Brain Oncogenesis

by A.G.M. Mostofa, Surendra R. Punganuru, Hanumantha Rao Madala, Mohammad Al-Obaide and Kalkunte S. Srivenugopal

Biomolecules 2017, 7(2), 34; https://doi.org/10.3390/biom7020034 - 27 Mar 2017

Cited by 90 | Viewed by 11229

Abstract

Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central [...] Read more.

Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers. The roles of reactive astrocytes, tumor associated microglia and macrophages, metabolic alterations, microsatellite instability, O⁶-methylguanine DNA methyltransferase (MGMT) DNA repair and epigenetic alterations mediated by the isocitrate dehydrogenase 1 (IDH1) mutations have been discussed. The inflammatory pathways with relevance to the brain cancer treatments have been highlighted. Full article

(This article belongs to the Special Issue DNA Methylation and Cancer)

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Biomolecules, Volume 7, Issue 2 (June 2017) – 11 articles

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