scholarly journals Unique structure and function of viral rhodopsins

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Dmitry Bratanov ◽  
Kirill Kovalev ◽  
Jan-Philipp Machtens ◽  
Roman Astashkin ◽  
Igor Chizhov ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Structure And Function ◽  
Proton Donor ◽  
Dna Viruses ◽  
Host Interactions ◽  
Hydrophobic Barrier ◽  
High Resolution Structure ◽  
Group 2 ◽  
Marine Protists ◽  
And Function

Abstract Recently, two groups of rhodopsin genes were identified in large double-stranded DNA viruses. The structure and function of viral rhodopsins are unknown. We present functional characterization and high-resolution structure of an Organic Lake Phycodnavirus rhodopsin II (OLPVRII) of group 2. It forms a pentamer, with a symmetrical, bottle-like central channel with the narrow vestibule in the cytoplasmic part covered by a ring of 5 arginines, whereas 5 phenylalanines form a hydrophobic barrier in its exit. The proton donor E42 is placed in the helix B. The structure is unique among the known rhodopsins. Structural and functional data and molecular dynamics suggest that OLPVRII might be a light-gated pentameric ion channel analogous to pentameric ligand-gated ion channels, however, future patch clamp experiments should prove this directly. The data shed light on a fundamentally distinct branch of rhodopsins and may contribute to the understanding of virus-host interactions in ecologically important marine protists.

scholarly journals Cryo-EM structure and dynamics of the green-light absorbing proteorhodopsin

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stephan Hirschi ◽  
David Kalbermatter ◽  
Zöhre Ucurum ◽  
Thomas Lemmin ◽  
Dimitrios Fotiadis
Keyword(s):  
Proton Translocation ◽  
Functional Characterization ◽  
Green Light ◽  
Proton Donor ◽  
Molecular Organization ◽  
Primary Proton ◽  
Proton Pumps ◽  
Model Protein ◽  
Dynamics Simulations ◽  
And Function

AbstractThe green-light absorbing proteorhodopsin (GPR) is the archetype of bacterial light-driven proton pumps. Here, we present the 2.9 Å cryo-EM structure of pentameric GPR, resolving important residues of the proton translocation pathway and the oligomerization interface. Superposition with the structure of a close GPR homolog and molecular dynamics simulations reveal conformational variations, which regulate the solvent access to the intra- and extracellular half channels harbouring the primary proton donor E109 and the proposed proton release group E143. We provide a mechanism for the structural rearrangements allowing hydration of the intracellular half channel, which are triggered by changing the protonation state of E109. Functional characterization of selected mutants demonstrates the importance of the molecular organization around E109 and E143 for GPR activity. Furthermore, we present evidence that helices involved in the stabilization of the protomer interfaces serve as scaffolds for facilitating the motion of the other helices. Combined with the more constrained dynamics of the pentamer compared to the monomer, these observations illustrate the previously demonstrated functional significance of GPR oligomerization. Overall, this work provides molecular insights into the structure, dynamics and function of the proteorhodopsin family that will benefit the large scientific community employing GPR as a model protein.

scholarly journals Extensive morphological variability in asexually produced planktic foraminifera

2020 ◽  
Vol 6 (28) ◽  
pp. eabb8930 ◽  
Author(s):  
Catherine V. Davis ◽  
Caitlin M. Livsey ◽  
Hannah M. Palmer ◽  
Pincelli M. Hull ◽  
Ellen Thomas ◽  
...  
Keyword(s):  
Morphological Variability ◽  
Laboratory Culture ◽  
Structure And Function ◽  
Optimal Conditions ◽  
Temporal Response ◽  
Planktic Foraminifera ◽  
Neogloboquadrina Pachyderma ◽  
Marine Protists ◽  
And Function ◽  
Pelagic Ecosystems

Marine protists are integral to the structure and function of pelagic ecosystems and marine carbon cycling, with rhizarian biomass alone accounting for more than half of all mesozooplankton in the oligotrophic oceans. Yet, understanding how their environment shapes diversity within species and across taxa is limited by a paucity of observations of heritability and life history. Here, we present observations of asexual reproduction, morphologic plasticity, and ontogeny in the planktic foraminifer Neogloboquadrina pachyderma in laboratory culture. Our results demonstrate that planktic foraminifera reproduce both sexually and asexually and demonstrate extensive phenotypic plasticity in response to nonheritable factors. These two processes fundamentally explain the rapid spatial and temporal response of even imperceptibly low populations of planktic foraminifera to optimal conditions and the diversity and ubiquity of these species across the range of environmental conditions that occur in the ocean.

scholarly journals Bacterial β-Kdo glycosyltransferases represent a new glycosyltransferase family (GT99)

2016 ◽  
Vol 113 (22) ◽  
pp. E3120-E3129 ◽  
Author(s):  
Olga G. Ovchinnikova ◽  
Evan Mallette ◽  
Akihiko Koizumi ◽  
Todd L. Lowary ◽  
Matthew S. Kimber ◽  
...  
Keyword(s):  
Lipid A ◽  
Structure And Function ◽  
Crystallographic Structure ◽  
Core Oligosaccharide ◽  
Evolutionary Connection ◽  
Surface Polysaccharides ◽  
Cytidine Monophosphate ◽  
Group 2 ◽  
Raoultella Terrigena ◽  
And Function

Kdo (3-deoxy-d-manno-oct-2-ulosonic acid) is an eight-carbon sugar mostly confined to Gram-negative bacteria. It is often involved in attaching surface polysaccharides to their lipid anchors. α-Kdo provides a bridge between lipid A and the core oligosaccharide in all bacterial LPSs, whereas an oligosaccharide of β-Kdo residues links “group 2” capsular polysaccharides to (lyso)phosphatidylglycerol. β-Kdo is also found in a small number of other bacterial polysaccharides. The structure and function of the prototypical cytidine monophosphate-Kdo–dependent α-Kdo glycosyltransferase from LPS assembly is well characterized. In contrast, the β-Kdo counterparts were not identified as glycosyltransferase enzymes by bioinformatics tools and were not represented among the 98 currently recognized glycosyltransferase families in the Carbohydrate-Active Enzymes database. We report the crystallographic structure and function of a prototype β-Kdo GT from WbbB, a modular protein participating in LPS O-antigen synthesis inRaoultella terrigena. The β-Kdo GT has dual Rossmann-fold motifs typical of GT-B enzymes, but extensive deletions, insertions, and rearrangements result in a unique architecture that makes it a prototype for a new GT family (GT99). The cytidine monophosphate-binding site in the C-terminal α/β domain closely resembles the corresponding site in bacterial sialyltransferases, suggesting an evolutionary connection that is not immediately evident from the overall fold or sequence similarities.

scholarly journals Relationship between plasma aldosterone and left ventricular structure and function in patients with heart failure with preserved ejection fraction

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
A. N. Shevelok
Keyword(s):  
Odds Ratio ◽  
Left Ventricular ◽  
Structure And Function ◽  
Plasma Aldosterone ◽  
Preserved Ejection Fraction ◽  
Concentric Hypertrophy ◽  
Group 2 ◽  
Lv Diastolic Dysfunction ◽  
And Function ◽  
Group 1

Aim. To study the relationship between plasma aldosterone level and left ventricular (LV) structure and function in heart failure with preserved ejection fraction (HFpEF).Material and methods. This prospective study included 158 patients (58 men and 100 women, mean age, 62,3±7,4 years) with compensated HFpEF. Patients had no history of primary aldosteronism and did not use the mineralocorticoid receptor antagonists during the last 6 weeks. The plasma aldosterone was determined by enzyme immunoassay in all patients and the severity of structural and functional cardiac changes was assessed. The concentration of 40160 pg/ml was considered the reference values. Assessment of cardiac structure and function was carried out using transthoracic echocardiography.Results. According to the laboratory results, all patients were divided into two groups: group 1 — 99 (62,7%) patients (95% confidence interval (CI), 55,0-70,0%) with normal aldosterone levels; group 2 — 59 (37,3%) patients (95% Cl, 30,0-45,0%) with hyperaldosteronism. End-diastolic volume, left atrial volume, LV mass index, severity of LV diastolic dysfunction and the prevalence of concentric hypertrophy were significantly higher in group 2 patients compared with group 1 (p<0,05 for all). Blood aldosterone levels positively correlated with E/e’ (r=0,63, p<0,001). Regression analysis, adjusted for age and comorbidity, demonstrated that plasma aldosterone levels were closely associated with E/e’ (odds ratio, 3,42; 95% CI, 1,65-9,64, p=0,001) and LV concentric hypertrophy (odds ratio, 1,12; 95% CI, 1,08-3,16, p=0,042).Conclusion. The development of secondary hyperaldosteronism in patients with HFpEF is an independent predictor of LV diastolic dysfunction and unfavorable prognostic types of LV remodeling.

scholarly journals Ultrasonography to detect cardiovascular damage in children with essential hypertension

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Liu ◽  
Cui Hou ◽  
Miao Hou ◽  
Qiu-Qin Xu ◽  
Hui Wang ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Blood Vessels ◽  
Pulse Wave ◽  
Left Ventricular ◽  
Structure And Function ◽  
Healthy Children ◽  
Group 3 ◽  
Group 2 ◽  
And Function ◽  
Group 1

Abstract Background Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography. Methods All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid–femoral pulse wave velocity (cfPWV), intimal–medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography. Results The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E’ among three groups. Conclusion Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

scholarly journals Structural and Functional Characterization of G Protein-Coupled Receptors with Deep Mutational Scanning

2019 ◽  
Author(s):  
Eric M. Jones ◽  
Nathan B. Lubock ◽  
AJ Venkatakrishnan ◽  
Jeffrey Wang ◽  
Alex M. Tseng ◽  
...  
Keyword(s):  
G Protein ◽  
Drug Targets ◽  
Functional Characterization ◽  
Structure And Function ◽  
G Protein Coupled Receptors ◽  
Single Amino Acid ◽  
Loss Of Function ◽  
And Function ◽  
Drug Receptors ◽  
G Protein Coupled

AbstractIn humans, the 813 G protein-coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state, and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here we developed a platform to characterize large libraries of GPCR variants in human cell lines with a barcoded transcriptional reporter of G-protein signal transduction. We tested 7,800 of 7,828 possible single amino acid substitutions to the beta-2 adrenergic receptor (β2AR) at four concentrations of the agonist isoproterenol. We identified residues specifically important for β2AR signaling, mutations in the human population that are potentially loss of function, and residues that modulate basal activity. Using unsupervised learning, we resolve residues critical for signaling, including all major structural motifs and molecular interfaces. We also find a previously uncharacterized structural latch spanning the first two extracellular loops that is highly conserved across Class A GPCRs and is conformationally rigid in both the inactive and active states of the receptor. More broadly, by linking deep mutational scanning with engineered transcriptional reporters, we establish a generalizable method for exploring pharmacogenomics, structure and function across broad classes of drug receptors.

scholarly journals Effects of chronic airway obstruction and atrial fibrillation on the cardiac structure and function in patients with heart failure

2020 ◽  
Vol 25 (2) ◽  
pp. 60-67
Author(s):  
A. I. Chesnikova ◽  
T. A. Dzyurich ◽  
V. A. Safronenko ◽  
O. E. Kolomatskaya ◽  
A. Yu. Batalina
Keyword(s):  
Airway Obstruction ◽  
Cardiac Remodeling ◽  
Structure And Function ◽  
Area Index ◽  
Group 3 ◽  
Cardiac Structure And Function ◽  
Group 2 ◽  
And Function ◽  
Experimental Group ◽  
Chronic Airway

Aim. To study the cardiac remodeling in heart failure (HF) patients with atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD).Material and methods. The study included 120 patients who were divided into 4 groups: the experimental group — patients with HF, AF and COPD (n=29), group 1 — patients with COPD, without cardiovascular disease (n=28), group 2 — patients with HF and COPD, without AF (n=30), group 3 — patients with HF and AF, without COPD (n=33). All patients underwent echocardiography using the MyLab70 Ultrasound System (Esaote, Italy).Results. In comparison with patients of group 3, patients of the experimental group had lower left and right atrial volumes (p=0,001 and p=0,004, respectively), higher right ventricular (RV) wall thickness (p<0,001), lower RV end-diastolic area index (p=0,007) and fractional area change (FAC) (p=0б011), which indicates the effect of chronic airway obstruction on cardiac remodeling in patients with combination of these pathologies. In comparison with patients of group 2, patients of the experimental group had significantly larger RV dimension (p=0,012) and higher RV endsystolic area index (p<0,001), as well as lower systolic RV function (ejection fraction (p=0,002), FAC (p<0,001), tricuspid annular plane systolic excursion (p=0,012)) and higher pressure in the pulmonary circulation (p=0,001). This is due to high hemodynamic load on the RV related to AF and chronic airway obstruction.Conclusion. The results of the study revealed features of cardiac remodeling pathogenesis in HF patients with AF and COPD. Comparative analysis of the results made it possible to indicate different mechanisms underlying AF, to assess the effects of both AF and chronic airway obstruction on the cardiac structure and function in patients with HF and combination of these pathologies.

Assembly of adenovirus-specific nuclear inclusions in lytically infected HeLa cells: an ultrastructural and cytochemical study

1993 ◽  
Vol 71 (9-10) ◽  
pp. 475-487 ◽  
Author(s):  
Nathalie Chaly ◽  
Xia Chen
Keyword(s):  
Nuclear Dna ◽  
Chromatin Condensation ◽  
Structure And Function ◽  
Nuclear Inclusions ◽  
Dna Viruses ◽  
Cytochemical Study ◽  
Nuclear Ultrastructure ◽  
Interchromatin Granule ◽  
Nucleolar Volume ◽  
And Function

Adenoviruses (Ads) are nuclear DNA viruses that remodel host nuclear structure and function and induce formation of a variety of nuclear inclusions within which Ad DNA is replicated and transcribed. In this study, we have examined inclusion assembly by electron microscopy of samples stained conventionally or with bismuth to detect phosphoproteins. Small dense fibrillar bodies (DFBs) appeared very early associated with interchromatin granule (ICG) clusters. Somewhat later, similar DFBs lay near amorphous, loosely fibrillar structures that were moderately electron dense and showed little bismuth deposition. These clear fibrillar bodies (CFBs) enlarged and DFBs became embedded in their surface. At later stages, CFBs and DFBs were again dissociated. DFBs seen very early were poor in phosphoproteins, but later DFBs, whether embedded in the CFBs or lying near them, were intensely bismuth stained. DFBs and CFBs were less prominent once assembled virions were seen. At this late stage, virions were generally associated with moderately dense, slightly bismuth positive, irregularly shaped fibrillar inclusions that have previously been identified as viral genome storage sites. In addition, very dense fibrillar bodies, consisting usually of an electron-dense fibrillar shell and a less dense fibrogranular core, were observed at all but the earliest stages of infection, often at some distance from CFBs. There was also a major reorganization of host components during infection, including chromatin condensation, reduction of nucleolar volume and aggregation of the fibrillar regions at the nucleolar surface, and increased prominence of ICG clusters. A model is proposed for the assembly of Ad replication factories.Key words: adenovirus, lytic infection, replication factories, nuclear ultrastructure, cytochemistry.

The histidine phosphatase superfamily: structure and function

2007 ◽  
Vol 409 (2) ◽  
pp. 333-348 ◽  
Author(s):  
Daniel J. Rigden
Keyword(s):  
Sequence Similarity ◽  
Structure And Function ◽  
Proton Donor ◽  
Phosphoglycerate Mutase ◽  
Catalytic Core ◽  
Potential Applications ◽  
History Of ◽  
Histidine Phosphatase Superfamily ◽  
And Function ◽  
Functionally Diverse

The histidine phosphatase superfamily is a large functionally diverse group of proteins. They share a conserved catalytic core centred on a histidine which becomes phosphorylated during the course of the reaction. Although the superfamily is overwhelmingly composed of phosphatases, the earliest known and arguably best-studied member is dPGM (cofactor-dependent phosphoglycerate mutase). The superfamily contains two branches sharing very limited sequence similarity: the first containing dPGM, fructose-2,6-bisphosphatase, PhoE, SixA, TIGAR [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator], Sts-1 and many other activities, and the second, smaller, branch composed mainly of acid phosphatases and phytases. Human representatives of both branches are of considerable medical interest, and various parasites contain superfamily members whose inhibition might have therapeutic value. Additionally, several phosphatases, notably the phytases, have current or potential applications in agriculture. The present review aims to draw together what is known about structure and function in the superfamily. With the benefit of an expanding set of histidine phosphatase superfamily structures, a clearer picture of the conserved elements is obtained, along with, conversely, a view of the sometimes surprising variation in substrate-binding and proton donor residues across the superfamily. This analysis should contribute to correcting a history of over- and mis-annotation in the superfamily, but also suggests that structural knowledge, from models or experimental structures, in conjunction with experimental assays, will prove vital for the future description of function in the superfamily.

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