Desulfovibrio marinus single-subunit oligosaccharyltransferase and its human IgG substrates
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Eclipse
ORGANISM(S): Escherichia Coli (ncbitaxon:562) Homo Sapiens (ncbitaxon:9606) Desulfovibrio Marinus (ncbitaxon:370038)
SUBMITTER: 
Matthew P. DeLisa Parastoo Azadi
PROVIDER: MSV000098017 | MassIVE | Wed May 28 09:54:00 BST 2025
SECONDARY ACCESSION(S): PXD064379
REPOSITORIES: MassIVE
Publications
Discovery of a single-subunit oligosaccharyltransferase that enables glycosylation of full-length IgG antibodies in bacteria.
Sotomayor Belen B Donahue Thomas C TC Mahajan Sai Pooja SP Taw May N MN Hulbert Sophia W SW Bidstrup Erik J EJ Owitipana D Natasha DN Pang Alexandra A Yang Xu X Ghosal Souvik S Alabi Christopher A CA Azadi Parastoo P Gray Jeffrey J JJ Jewett Michael C MC Wang Lai-Xi LX DeLisa Matthew P MP
Nature communications 20250704 1
Human immunoglobulin G (IgG) antibodies are a major class of biotherapeutics and undergo N-linked glycosylation in their Fc domain, which is critical for immune functions and therapeutic activity. Hence, technologies for producing authentically glycosylated IgGs are in high demand. Previous attempts to engineer Escherichia coli for this purpose have met limited success due in part to the lack of oligosaccharyltransferase (OST) enzymes that can install N-glycans at the conserved N297 site in the ...[more]
Similar Datasets
Project description:As one of the most important post-translational protein modifications, lysine acetylation is catalyzed by lysine acetyltransferases (KATs), which catalyze the covalent attachment of an acetyl group to the N epsilon–residue of lysine. The histone acetyltransferase MOF, which represents the main histone H4 lysine-16 specific acetyltransferase, is the KAT subunit of two mutually exclusive multiprotein complexes in metazoa, namely the MSL (male-specific lethal) and the NSL (non-specific lethal) complex. Depletion of both, MOF and the NSL complex subunit Kansl2 result in selective changes of the cellular acetylome. As a consequence, modulation of nuclear lamin lysine acetylations correlate with profound changes in nuclear morphology, like micronuclei formation.
2023-01-05 | PXD038521 | Pride
Project description:An uncharacterized marine bacterium
| PRJNA16658 | ENA
Project description:The sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough possesses four periplasmic hydrogenases to facilitate the oxidation of molecular hydrogen. These include an [Fe], a [NiFeSe] and two [NiFe] hydrogenases encoded by the hyd, hys, hyn1 and hyn2 genes, respectively. In order to understand their cellular functions the expression levels of these hydrogenases, along with the growth rate analysis of mutant strains, was determined during growth on defined media under 3 different conditions. These conditions incuded lactate or hydrogen at either 5% or 50% (vol/vol) used as the sole electron donor for sulfate reduction. Keywords: Electron donor change
2007-07-02 | GSE8137 | GEO
Project description:Investigation of partial genome gene expression level changes in a Desulfovibrio africanus during exponential and stationary phase growth in the presence and absence of 5 ug/L Hg2+ (as HgNO3). Desulfovibrio africanus is a known mercury methylating bacteria A 3 chip study using total RNA recovered from three separate cultures of Desulfovibrio africanus with 5 ug/L Hg during exponential phase growth, three seperate cultures of Desulfovibrio africanus with 5 ug/L Hg during stationary phase growth, three cultures of Desulfovibrio africanus without Hg during exponential phase growth, and Desulfovibrio africanus without Hg during stationary phase growth. Each chip measures the expression level of 4,585 genes and intergenic regions from Desulfovibrio africanus strain Walvis Bay on a custom Nimblegen format with 75-mer probes with tiled in 4-plex format.
2012-06-06 | E-GEOD-32580 | biostudies-arrayexpress
Project description:The co-utilization of hexoses and pentoses derived from lignocellulose is an attractive trait for in microorganisms considered for consolidated biomass processing to biofuels. This issue was examined for the H2-producing, extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus growing on oligosaccharides (composed of glucose and xylose) compared to monosaccharides. Based on the whole-genome transcriptional response analysis and comparative genomics, carbohydrate specificities for transport systems could be proposed for a number of the 24 putative carbohydrate ATP-binding cassette (ABC) transporters in the C. saccharolyticus genome. Transcriptome analysis showed different transporters were utilized for uptake of oligosaccharides than those used for monosaccharides uptake. No evidence for catabolite repression was noted for either growth on multi-sugar mixtures or in the corresponding transcriptomes.
2009-12-29 | GSE17427 | GEO
Project description:AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.
| S-EPMC8491978 | biostudies-literature
Project description:Attachment of lipids to proteins is a key form of protein modification which intersects with all areas of cellular physiology 1 . Of these, the most pervasive form of protein lipidation is protein S-acylation, also commonly known as protein palmitoylation. Protein palmitoylation is a post-translational modification whereby long chain fatty acids, most typically the 16-carbon palmitic acid, is attached to a cytosol-facing cysteine through a thioester linkage. More than 10% of the proteome is targeted by this modification2, which is catalyzed by members of the zDHHC family of integral membrane enzymes. In humans, there are 23 members of the zDHHC family localized at a variety of organellar membranes as well as the plasma membrane that catalyze protein palmitoylation. Despite having been discovered more than twenty years ago 3 4 the chemistry and biology of many of the zDHHC members remain poorly understood and for several members, few substrates have been characterized. Intriguingly, there are no primary sequence determinants that dictate sites of protein palmitoylation. Cysteines that are proximal to the membrane have a high propensity of being palmitoylated.
2023-10-04 | PXD041525 | Pride
Project description:To examine the effects of Desulfovibrio on L cells, L cells from antibiotic-treated and Desulfovibrio-colonized B6.Cg-Gcgtm1.1(cre/GFP)Rpa/J (Gcg-Cre:GFP) mice were isolated and subjected to scRNA-seq.
2024-05-06 | GSE220937 | GEO
Project description:Ibrahim2008 - Mitotic Spindle Assembly Checkpoint - Dissociation variant
The Mitotic Spindle Assembly Checkpoint ((M)SAC) is an evolutionary conserved mechanism. This model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. MCC:APC dissociation is described by two alternatives models, namely the "Dissociation" and the "Convey" model variants. Both these model are available in BioModels Database. This model corresponds to the "Dissociation" variant.
This model is described in the article:
In-silico modeling of the mitotic spindle assembly checkpoint.
Ibrahim B, Diekmann S, Schmitt E, Dittrich P
PLoS One. 2008 Feb 6;3(2):e1555.
Abstract:
BACKGROUND: The Mitotic Spindle Assembly Checkpoint ((M)SAC) is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. Its malfunction can lead to cancer.
PRINCIPLE FINDINGS: We have constructed and validated for the human (M)SAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. The model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the (M)SAC are derived. Most of the kinetic constants are taken from literature, the remaining four unknown parameters are derived by an evolutionary optimization procedure for an objective function describing the dynamics of the APC:Cdc20 complex. MCC:APC dissociation is described by two alternatives, namely the "Dissociation" and the "Convey" model variants. The attachment of the kinetochore to microtubuli is simulated by a switching parameter silencing those reactions which are stopped by the attachment. For both, the Dissociation and the Convey variants, we compare two different scenarios concerning the microtubule attachment dependent control of the dissociation reaction. Our model is validated by simulation of ten perturbation experiments.
CONCLUSION: Only in the controlled case, our models show (M)SAC behaviour at meta- to anaphase transition in agreement with experimental observations. Our simulations revealed that for (M)SAC activation, Cdc20 is not fully sequestered; instead APC is inhibited by MCC binding.
This model describes the controlled dissociation variant of the mitotic spindle assembly checkpoint. If the tool you use has problems with events, you can uncomment the assignment rules for u and u_prime and comment out the list of events.
In accordance with the authors due to typos in the original publication some initial conditions and parameters were slightly changed in the model:
article
model
[O-Mad2]
1.5e-7 M
1.3e-7 M
[BubR1:Bub3]
1.30e-7 M
1.27e-7 M
k -4
0.01 M -1
s -1
0.02 M -1
s -1
k -5
0.1 M -1
s -1
0.2 M -1
s -1
This model is hosted on BioModels Database
and identified by: MODEL6655615431
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000186 | BioModels
Project description:Ibrahim2008 - Mitotic Spindle Assembly Checkpoint - Convey variant
The Mitotic Spindle Assembly Checkpoint ((M)SAC) is an evolutionary conserved mechanism. This model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. MCC:APC dissociation is described by two alternatives models, namely the "Dissociation" and the "Convey" model variants. Both these model are available in BioModels Database. This model corresponds to the "Convey" variant.
This model is described in the article:
In-silico modeling of the mitotic spindle assembly checkpoint.
Ibrahim B, Diekmann S, Schmitt E, Dittrich P
PLoS One. 2008 Feb 6;3(2):e1555.
Abstract:
BACKGROUND: The Mitotic Spindle Assembly Checkpoint ((M)SAC) is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. Its malfunction can lead to cancer.
PRINCIPLE FINDINGS: We have constructed and validated for the human (M)SAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. The model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the (M)SAC are derived. Most of the kinetic constants are taken from literature, the remaining four unknown parameters are derived by an evolutionary optimization procedure for an objective function describing the dynamics of the APC:Cdc20 complex. MCC:APC dissociation is described by two alternatives, namely the "Dissociation" and the "Convey" model variants. The attachment of the kinetochore to microtubuli is simulated by a switching parameter silencing those reactions which are stopped by the attachment. For both, the Dissociation and the Convey variants, we compare two different scenarios concerning the microtubule attachment dependent control of the dissociation reaction. Our model is validated by simulation of ten perturbation experiments.
CONCLUSION: Only in the controlled case, our models show (M)SAC behaviour at meta- to anaphase transition in agreement with experimental observations. Our simulations revealed that for (M)SAC activation, Cdc20 is not fully sequestered; instead APC is inhibited by MCC binding.
This model describes the controlled dissociation variant of the mitotic spindle assembly checkpoint. If the tool you use has problems with events, you can uncomment the assignment rules for u and u_prime and comment out the list of events.
In accordance with the authors due to typos in the original publication some initial conditions and parameters were slightly changed in the model:
article
model
[O-Mad2]
1.5e-7 M
1.3e-7 M
[BubR1:Bub3]
1.30e-7 M
1.27e-7 M
k -4
0.01 M -1
s -1
0.02 M -1
s -1
k -5
0.1 M -1
s -1
0.2 M -1
s -1
This model is hosted on BioModels Database
and identified by: MODEL6655578762
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000187 | BioModels