Evaluation of Effects of Fc Domain High-Mannose Glycan on Antibody Stability

2012 ◽  
Vol 101 (11) ◽  
pp. 4107-4117 ◽  
Author(s):  
Yuefeng Lu ◽  
Kimberly Westland ◽  
Yu-heng Ma ◽  
Himanshu Gadgil
Keyword(s):  
High Mannose ◽  
High Mannose Glycan

Effect of high mannose glycan pairing on IgG antibody clearance

Biologicals ◽  
2016 ◽  
Vol 44 (3) ◽  
pp. 163-169 ◽  
Author(s):  
Yaoqing Diana Liu ◽  
Gregory C. Flynn
Keyword(s):  
Igg Antibody ◽  
High Mannose ◽  
High Mannose Glycan

Effect of Transferrin on the Degradation of Glycoproteins Bearing a Hybrid or High-Mannose Glycan by Alveolar Macrophages

1994 ◽  
Vol 215 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Maria Janicka ◽  
Paul A. Chindemi ◽  
Wei-Li Hu ◽  
Erwin Regoeczi
Keyword(s):  
Alveolar Macrophages ◽  
High Mannose ◽  
High Mannose Glycan

scholarly journals Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Lisa M. Parsons ◽  
Yanming An ◽  
Li Qi ◽  
Mitchell R. White ◽  
Roosmarijn van der Woude ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pulmonary Surfactant ◽  
Three Dimensional ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Human Populations ◽  
Head Region ◽  
High Mannose ◽  
Pulmonary Surfactant Protein ◽  
High Mannose Glycan

ABSTRACT Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D). Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes. These can pose a pandemic threat through reassortment and emergence in human populations. Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value. Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype. Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site. Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8. Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data. We found that glycosite “N165” (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs. SP-D was not active on LPAIV but was on H3 HAs. Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes. Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis. IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype. Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s). While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks. Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.

scholarly journals Cryo–electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B

Science ◽  
2019 ◽  
Vol 366 (6471) ◽  
pp. 1372-1375 ◽  
Author(s):  
Ana S. Ramírez ◽  
Julia Kowal ◽  
Kaspar P. Locher
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Secretory Proteins ◽  
Catalytic Subunits ◽  
Protein Substrates ◽  
Cryo Electron Microscopy ◽  
Structural Differences ◽  
High Mannose ◽  
Equivalent Region ◽  
High Mannose Glycan

Oligosaccharyltransferase (OST) catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum. Mammals express two distinct OST complexes that act in a cotranslational (OST-A) or posttranslocational (OST-B) manner. Here, we present high-resolution cryo–electron microscopy structures of human OST-A and OST-B. Although they have similar overall architectures, structural differences in the catalytic subunits STT3A and STT3B facilitate contacts to distinct OST subunits, DC2 in OST-A and MAGT1 in OST-B. In OST-A, interactions with TMEM258 and STT3A allow ribophorin-I to form a four-helix bundle that can bind to a translating ribosome, whereas the equivalent region is disordered in OST-B. We observed an acceptor peptide and dolichylphosphate bound to STT3B, but only dolichylphosphate in STT3A, suggesting distinct affinities of the two OST complexes for protein substrates.

Cell culture media supplemented with raffinose reproducibly enhances high mannose glycan formation

2017 ◽  
Vol 252 ◽  
pp. 32-42 ◽  
Author(s):  
David Brühlmann ◽  
Anais Muhr ◽  
Rebecca Parker ◽  
Thomas Vuillemin ◽  
Blanka Bucsella ◽  
...  
Keyword(s):  
Cell Culture ◽  
Culture Media ◽  
Cell Culture Media ◽  
High Mannose ◽  
High Mannose Glycan

scholarly journals Isomer Information from Ion Mobility Separation of High-Mannose Glycan Fragments

2018 ◽  
Vol 29 (5) ◽  
pp. 972-988 ◽  
Author(s):  
David J. Harvey ◽  
Gemma E. Seabright ◽  
Snezana Vasiljevic ◽  
Max Crispin ◽  
Weston B. Struwe
Keyword(s):  
Ion Mobility ◽  
Mobility Separation ◽  
High Mannose ◽  
Ion Mobility Separation ◽  
High Mannose Glycan

Metabolic markers associated with high mannose glycan levels of therapeutic recombinant monoclonal antibodies

2015 ◽  
Vol 203 ◽  
pp. 22-31 ◽  
Author(s):  
Sohye Kang ◽  
Zhongqi Zhang ◽  
Jason Richardson ◽  
Bhavana Shah ◽  
Shivani Gupta ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Metabolic Markers ◽  
High Mannose ◽  
High Mannose Glycan

Influence of high-mannose glycan whose glucose moiety is substituted with 5-thioglucose on calnexin/calreticulin cycle

RSC Advances ◽  
2016 ◽  
Vol 6 (80) ◽  
pp. 76879-76882 ◽  
Author(s):  
Masafumi Sakono ◽  
Akira Seko ◽  
Yoichi Takeda ◽  
Masakazu Hachisu ◽  
Akihiko Koizumi ◽  
...  
Keyword(s):  
Glycosyl Donor ◽  
High Mannose ◽  
High Mannose Glycan

Our study first revealed that UDP-5-thioglucose functions as a glycosyl donor of UDP-glucose: glycoprotein glucosyltransferase to produce 5-thio-glucosylated Man9 (5S-G1M9).

The Influence of Carbohydrate Structure on the Clearance of Recombinant Tissue-Type Plasminogen Activator

1988 ◽  
Vol 60 (02) ◽  
pp. 255-261 ◽  
Author(s):  
A Hotchkiss ◽  
C J Refino ◽  
C K Leonard ◽  
J V O'Connor ◽  
C Crowley ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plasminogen Activator ◽  
Sodium Periodate ◽  
Glycosylation Site ◽  
Tissue Type ◽  
Carbohydrate Structure ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
High Mannose ◽  
Oligosaccharide Structures

SummaryModification of the carbohydrate structures of recombinant tissue-type plasminogen activator (rt-PA) can increase or decrease its rate of clearance in rabbits. When rt-PA was treated with sodium periodate to oxidize carbohydrate residues, the rate of clearance was decreased from 9.6 ± 1.9 ml min−1 kg−1 to 3.5 ± 0.6 ml min−1 kg−1 (mean ± SD, n = 5). A similar change in the clearance of rt-PA was introduced by the use of endo-β-N-acetyl- glucosaminidase H (Endo-H), which selectively removes high mannose asparagine-linked oligosaccharides; the clearance of Endo-H-treated rt-PA was 5.0 ± 0.5 ml min−1 kg−1. A mutant of rt-PA was produced with an amino acid substitution at position 117 (Asn replaced with Gin) to remove a potential glycosylation site that normally contains a high mannose structure. The clearance of this material was also decreased, similar to the periodate and Endo-H-treated rt-PA. Conversely, when rt-PA was produced in the CHO 15B cell line, which can produce only high mannose oligosaccharide structures on glycoproteins, the clearance was increased by a factor of 1.8. These results demonstrate that the removal of rt-PA from the blood depends significantly upon the nature of its oligosaccharide structures.

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