LOF and GOF Alleles Shed Light on the Molecular Basis of phyB Signaling in Plants

Apocarotenoids are important signaling molecules generated from carotenoids through the action of carotenoid cleavage dioxygenases (CCDs). These enzymes have a remarkable ability to cleave carotenoids at specific alkene bonds while leaving chemically similar sites within the polyene intact. Although several bacterial and eukaryotic CCDs have been characterized, the long-standing goal of experimentally visualizing a CCD–carotenoid complex at high resolution to explain this exquisite regioselectivity remains unfulfilled. CCD genes are also present in some archaeal genomes, but the encoded enzymes remain uninvestigated. Here, we address this knowledge gap through analysis of a metazoan-like archaeal CCD fromCandidatusNitrosotalea devanaterra (NdCCD).NdCCD was active toward β-apocarotenoids but did not cleave bicyclic carotenoids. It exhibited an unusual regiospecificity, cleaving apocarotenoids solely at the C14′–C13′ alkene bond to produce β-apo-14′-carotenals. The structure ofNdCCD revealed a tapered active site cavity markedly different from the broad active site observed for the retinal-formingSynechocystisapocarotenoid oxygenase (SynACO) but similar to the vertebrate retinoid isomerase RPE65. The structure ofNdCCD in complex with its apocarotenoid product demonstrated that the site of cleavage is defined by interactions along the substrate binding cleft as well as selective stabilization of reaction intermediates at the scissile alkene. These data on the molecular basis of CCD catalysis shed light on the origins of the varied catalytic activities found in metazoan CCDs, opening the possibility of modifying their activity through rational chemical or genetic approaches.

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Autophagy: An Essential Degradation Program for Cellular Homeostasis and Life

Cells ◽

10.3390/cells7120278 ◽

2018 ◽

Vol 7 (12) ◽

pp. 278 ◽

Cited By ~ 54

Author(s):

Yoomi Chun ◽

Joungmok Kim

Keyword(s):

Neurodegenerative Diseases ◽

Molecular Basis ◽

Wide Spectrum ◽

Regulatory Mechanisms ◽

Cellular Homeostasis ◽

Post Translational Modifications ◽

Cellular Stresses ◽

Shed Light ◽

Novel Therapeutic

Autophagy is a lysosome-dependent cellular degradation program that responds to a variety of environmental and cellular stresses. It is an evolutionarily well-conserved and essential pathway to maintain cellular homeostasis, therefore, dysfunction of autophagy is closely associated with a wide spectrum of human pathophysiological conditions including cancers and neurodegenerative diseases. The discovery and characterization of the kingdom of autophagy proteins have uncovered the molecular basis of the autophagy process. In addition, recent advances on the various post-translational modifications of autophagy proteins have shed light on the multiple layers of autophagy regulatory mechanisms, and provide novel therapeutic targets for the treatment of the diseases.

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The Molecular Mechanism of Rhein in Diabetic Nephropathy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/487097 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Cong-Cong Zeng ◽

Xi Liu ◽

Guo-Rong Chen ◽

Qian-Jia Wu ◽

Wang-Wang Liu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Molecular Basis ◽

Active Role ◽

Protective Role ◽

Medical Data ◽

Kidney Protection ◽

Shed Light ◽

Chinese Medicinal Plant

Diabetic nephropathy (DN) is characterized by unclear pathogenesis. Recent medical data shows that the incidence of DN rises year by year. Rhein is the main compositions of rhubarb, a traditional Chinese medicinal plant, which plays an active role in kidney protection. The prophylaxis and phytotherapeutic effects of rhein are due to its anti-inflammatory and antifibrosis properties. Here, we shed light on the renal protective role of rhein in diabetes mellitus (DM) with a particular focus on the molecular basis of this effect.

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Sequestration to lipid droplets promotes histone availability by preventing turnover of excess histones

10.1101/2020.08.06.237164 ◽

2020 ◽

Author(s):

Roxan A. Stephenson ◽

Jonathon M. Thomalla ◽

Lili Chen ◽

Petra Kolkhof ◽

Mathias Beller ◽

...

Keyword(s):

Molecular Basis ◽

Lipid Droplets ◽

Quantitative Imaging ◽

Nurse Cells ◽

Intercellular Transport ◽

Fat Storage ◽

Tightly Coupled ◽

Histone Synthesis ◽

Insight Into ◽

Shed Light

AbstractBecause dearth and overabundance of histones result in cellular defects, histone synthesis and demand are typically tightly coupled. In Drosophila embryos, histones H2B/H2A/H2Av accumulate on lipid droplets (LDs), cytoplasmic fat storage organelles. Without this binding, maternally provided H2B/H2A/H2Av are absent; however, the molecular basis of how LDs ensure histone storage is unclear. Using quantitative imaging, we uncover when during oogenesis these histones accumulate, and which step of accumulation is LD-dependent. LDs originate in nurse cells and are transported to the oocyte. Although H2Av accumulates on LDs in nurse cells, the majority of the final H2Av pool is synthesized in oocytes. LDs promote intercellular transport of the histone-anchor Jabba and thus its presence in the ooplasm. Jabba prevents ooplasmic H2Av from degradation, safeguarding the H2Av stockpile. Our findings provide insight into the mechanism for establishing histone stores during Drosophila oogenesis and shed light on the function of LDs as protein-sequestration sites.

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Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2

Cell Discovery ◽

10.1038/s41421-020-00210-9 ◽

2020 ◽

Vol 6 (1) ◽

Cited By ~ 3

Author(s):

Lili Wu ◽

Qian Chen ◽

Kefang Liu ◽

Jia Wang ◽

Pengcheng Han ◽

...

Keyword(s):

Electron Microscopy ◽

Intermediate Host ◽

Molecular Basis ◽

Binding Mode ◽

Domestic Animals ◽

Broad Host Range ◽

Receptor Binding Domain ◽

Wild Animals ◽

Cryo Electron Microscopy ◽

Shed Light

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the recent pandemic COVID-19, is reported to have originated from bats, with its intermediate host unknown to date. Here, we screened 26 animal counterparts of the human ACE2 (hACE2), the receptor for SARS-CoV-2 and SARS-CoV, and found that the ACE2s from various species, including pets, domestic animals and multiple wild animals, could bind to SARS-CoV-2 receptor binding domain (RBD) and facilitate the transduction of SARS-CoV-2 pseudovirus. Comparing to SARS-CoV-2, SARS-CoV seems to have a slightly wider range in choosing its receptor. We further resolved the cryo-electron microscopy (cryo-EM) structure of the cat ACE2 (cACE2) in complex with the SARS-CoV-2 RBD at a resolution of 3 Å, revealing similar binding mode as hACE2 to the SARS-CoV-2 RBD. These results shed light on pursuing the intermediate host of SARS-CoV-2 and highlight the necessity of monitoring susceptible hosts to prevent further outbreaks.

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Molecular basis of NB1 (HNA-2a, CD177) deficiency

Blood ◽

10.1182/blood.v99.11.4231 ◽

2002 ◽

Vol 99 (11) ◽

pp. 4231-4233 ◽

Cited By ~ 50

Author(s):

Karin Kissel ◽

Steffi Scheffler ◽

Mohammed Kerowgan ◽

Jürgen Bux

Keyword(s):

Polymerase Chain Reaction ◽

Molecular Basis ◽

Chain Reaction ◽

Specific Primers ◽

Specific Antibodies ◽

Polymerase Chain ◽

Immune Neutropenia ◽

Shed Light ◽

Negative Phenotype ◽

Specific Mrna

Alloimmunization to the neutrophil antigen NB1 (HNA-2a, CD177) can result in immune neutropenia and transfusion-related acute lung injury. Recently, we were able to elucidate the primary structure of NB1. To shed light also on the molecular basis of the NB1-negative phenotype, we studied the neutrophils of 2 women with NB1-specific alloantibodies for intracellular and extracellular NB1 expression, NB1-specific mRNA production, and the presence of the NB1 gene. No antibody binding to neutrophils was observed by immunofluorescence and immunoblot using a variety of human and monoclonal NB1-specific antibodies. By reverse transcription–polymerase chain reaction with NB1-specific primers we could not detect NB1 cDNAs without accessory sequences, which were found to be introns. The NB1 gene was present in the genome of both patients. Our data indicate that the NB1-negative phenotype is the result of different off-frame insertions on RNA level, resulting in NB1 deficiency on neutrophils.

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Sulfatases and radical SAM enzymes: emerging themes in glycosaminoglycan metabolism and the human microbiota

Biochemical Society Transactions ◽

10.1042/bst20150191 ◽

2016 ◽

Vol 44 (1) ◽

pp. 109-115 ◽

Cited By ~ 20

Author(s):

Alhosna Benjdia ◽

Olivier Berteau

Keyword(s):

Human Physiology ◽

Molecular Basis ◽

Radical Sam ◽

Host Colonization ◽

Bacterial Populations ◽

Radical Sam Enzymes ◽

Human Microbiota ◽

Emerging Themes ◽

Glycosaminoglycan Metabolism ◽

Shed Light

Humans live in a permanent association with bacterial populations collectively called the microbiota. In the last 10 years, major advances in our knowledge of the microbiota have shed light on its critical roles in human physiology. The microbiota has also been shown to be a major factor in numerous pathologies including obesity or inflammatory disorders. Despite tremendous progresses, our understanding of the key functions of the human microbiota and the molecular basis of its interactions with the host remain still poorly understood. Among the factors involved in host colonization, two enzymes families, sulfatases and radical S-adenosyl-L-methionine enzymes, have recently emerged as key enzymes.

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Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry

10.1101/2020.07.29.227249 ◽

2020 ◽

Author(s):

Jorge Alberto Aguilar-Pineda ◽

Mazen Albaghdadi ◽

Wanlin Jiang ◽

Karin J. Vera Lopez ◽

Gonzalo Davila Del-Carpio ◽

...

Keyword(s):

Sex Hormones ◽

Protein Interactions ◽

Molecular Basis ◽

Severe Infection ◽

Cell Entry ◽

Spike Protein ◽

Female Sex ◽

Female Sex Hormones ◽

Shed Light ◽

Putative Mechanism

AbstractEmerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.

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Reverse Methanogenesis and Respiration in Methanotrophic Archaea

Archaea ◽

10.1155/2017/1654237 ◽

2017 ◽

Vol 2017 ◽

pp. 1-22 ◽

Cited By ~ 118

Author(s):

Peer H. A. Timmers ◽

Cornelia U. Welte ◽

Jasper J. Koehorst ◽

Caroline M. Plugge ◽

Mike S. M. Jetten ◽

...

Keyword(s):

Methane Oxidation ◽

Molecular Basis ◽

Electron Acceptors ◽

Genome Comparison ◽

Future Research ◽

Anaerobic Oxidation Of Methane ◽

Oxidation Of Methane ◽

Reverse Methanogenesis ◽

Methyl Coenzyme M Reductase ◽

Shed Light

Anaerobic oxidation of methane (AOM) is catalyzed by anaerobic methane-oxidizing archaea (ANME) via a reverse and modified methanogenesis pathway. Methanogens can also reverse the methanogenesis pathway to oxidize methane, but only during net methane production (i.e., “trace methane oxidation”). In turn, ANME can produce methane, but only during net methane oxidation (i.e., enzymatic back flux). Net AOM is exergonic when coupled to an external electron acceptor such as sulfate (ANME-1, ANME-2abc, and ANME-3), nitrate (ANME-2d), or metal (oxides). In this review, the reversibility of the methanogenesis pathway and essential differences between ANME and methanogens are described by combining published information with domain based (meta)genome comparison of archaeal methanotrophs and selected archaea. These differences include abundances and special structure of methyl coenzyme M reductase and of multiheme cytochromes and the presence of menaquinones or methanophenazines. ANME-2a and ANME-2d can use electron acceptors other than sulfate or nitrate for AOM, respectively. Environmental studies suggest that ANME-2d are also involved in sulfate-dependent AOM. ANME-1 seem to use a different mechanism for disposal of electrons and possibly are less versatile in electron acceptors use than ANME-2. Future research will shed light on the molecular basis of reversal of the methanogenic pathway and electron transfer in different ANME types.

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Renilla Bioluminescence: A Morphologic Approach to the Location of Photocytes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051050 ◽

1974 ◽

Vol 32 ◽

pp. 208-209

Author(s):

Ben O. Spurlock ◽

Milton J. Cormier

Keyword(s):

Excited State ◽

Ground State ◽

Molecular Basis ◽

Light Emission ◽

Chemical Basis ◽

Electronic Excited State ◽

Colonial Form ◽

The Common ◽

Eighteenth And Nineteenth Centuries ◽

Catalyzed Oxidation

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.

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