scholarly journals A conserved epitope on several human vitamin K-dependent proteins. Location of the antigenic site and influence of metal ions on antibody binding.

1988 ◽  
Vol 263 (13) ◽  
pp. 6259-6267 ◽  
Author(s):  
W R Church ◽  
T Messier ◽  
P R Howard ◽  
J Amiral ◽  
D Meyer ◽  
...  
Keyword(s):  
Metal Ions ◽  
Vitamin K ◽  
Antigenic Site ◽  
Antibody Binding ◽  
Conserved Epitope

scholarly journals A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aimin Tang ◽  
Zhifeng Chen ◽  
Kara S. Cox ◽  
Hua-Poo Su ◽  
Cheryl Callahan ◽  
...  
Keyword(s):  
Antigenic Site ◽  
Human Memory ◽  
Medical Need ◽  
Fusion Glycoprotein ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Parental Antibody ◽  
Conserved Epitope

Abstract Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parental antibody to MK-1654 which is currently in clinical development for the prevention of RSV infection in infants.

scholarly journals Inhibition of HER3 activation and tumor growth with a human antibody binding to a conserved epitope formed by domain III and IV

mAbs ◽  
2017 ◽  
Vol 9 (5) ◽  
pp. 831-843 ◽  
Author(s):  
Lisa C. Schmitt ◽  
Alexander Rau ◽  
Oliver Seifert ◽  
Jonas Honer ◽  
Meike Hutt ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Antibody Binding ◽  
Human Antibody ◽  
Domain Iii ◽  
Conserved Epitope

scholarly journals Discrimination of normal and abnormal prothrombin and protein C in plasma using a calcium ion-inhibited monoclonal antibody to a common epitope on several vitamin K-dependent proteins

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2418-2425 ◽  
Author(s):  
WR Church ◽  
FH Bhushan ◽  
KG Mann ◽  
EG Bovill
Keyword(s):  
Monoclonal Antibody ◽  
Vitamin K ◽  
Calcium Ion ◽  
Metal Ion ◽  
Protein C ◽  
Conformational Transition ◽  
Vitamin K Antagonists ◽  
Antigenic Site ◽  
Divalent Metal ◽  
Carboxyglutamic Acid

Abstract Vitamin K deficiency or administration of vitamin K antagonists results in the biosynthesis of abnormal des-gamma-carboxy forms of the vitamin K-dependent proteins. Monoclonal antibody H-11 binds several vitamin K- dependent proteins at a determinant that includes the first two residues of gamma-carboxyglutamic acid. Antibody H-11 binds fully carboxylated prothrombin and protein C in the presence of EDTA but binding is inhibited by the divalent metal ions, calcium, magnesium, and manganese. By contrast, des-gamma-carboxy prothrombin and protein C bind antibody H-11 the same in the presence of EDTA or calcium ion. Antibody H-11 thus appears to bind a conserved antigenic site containing gamma-carboxyglutamic acid that in the presence of divalent metal ion undergoes a conformational transition. This ability of antibody H-11 to bind des-gamma-carboxy prothrombin and protein C in the presence of calcium ion allowed the development of an immunoassay for these proteins in plasma. Prothrombin and protein C from stably anticoagulated individuals receiving warfarin were characterized by their ability to bind antibody H-11 in the presence of calcium ion. Binding of prothrombin and protein C to antibody H-11 in the presence of calcium correlated temporally with warfarin administration. The inability of calcium ion to inhibit binding of antibody H-11 to abnormal prothrombin and protein C in plasma suggests that the circulating forms of both proteins following warfarin administration cannot undergo the metal ion-dependent conformational transition that includes sequence residues 1 through 12.

Inhibition of vitamin K-dependent carboxylase by metal ions and metal complexes: A reassessment

1984 ◽  
Vol 228 (2) ◽  
pp. 646-652 ◽  
Author(s):  
Jolanta M. Kanabus-Kaminska ◽  
Jean-Marie Girardot
Keyword(s):  
Metal Ions ◽  
Metal Complexes ◽  
Vitamin K

A SHARED EPITOPE ON HUMAN PROTEIN C, FACTOR X, FACTOR VII, AND PROTTOBIN DEFINED BY A MONOCLONAL ANTIBODY

1987 ◽  
Author(s):  
W Church ◽  
T Messier ◽  
P Howard ◽  
J Amiral ◽  
D Meyer ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Vitamin K ◽  
Light Chain ◽  
Calcium Ion ◽  
Protein C ◽  
Solid Phase ◽  
Antigenic Site ◽  
Factor Vii ◽  
Factor X ◽  
Prothrombin Fragment

A monoclonal antibody prepared against hunan protein C (HPC) was found to react with several other vitamin K-dependent blood proteins. Using a competitive inhibition solid-phase radioinminoassay with HPC, binding of 125I-HPC to the antibody was inhibited by purified prothrombin, Factor X, and Factor VII in addition to protein C. Other vitamin K-dependent proteins including Factor IX, protein S, and bone-GLA protein did not compete for binding of 125I-HPC to the antibody. The effect of calciun ion on the binding of antibody to 125I-HPC was examined in a solid-phase imnunoassay system with the antibody bound to rabbit anti-mouse inminoglobulin adsorbed to microtiter plates. In the presence of 5 mM calciun ion, radiolabeled protein C did not bind to the antibody; radiolabeled protein C did bind, however, in the presence of 5 nM EDTA suggesting that the epitope is expressed only after removal of calciun ion. The antibody bound to prothrombin and to decarboxylated prothrombin after adsorption of the antigens onto nitrocellulose indicating that the presence of GLA was not required for antibody binding. Iimunoblotting of proteins which were reduced, the peptides separated by SDS-PAGE, and transferred to nitrocellulose showed that the antibody reacts with a determinant found on the light chains of protein C and Factor X and with prothrombin Fragment 1. Comparison of the protein sequences of protein C light chain, Factor X light chain, Factor VII, and prothrombin Fragment 1 identified a segment of amino acid sequence that is highly conserved in all four proteins and might contain the antigenic site. The monoclonal antibody thus defines an antigenic determinant which is masked by calcium ion and is found on the surface of several related, yet different coagulation proteins. This antibody should prove useful in understanding the evolutionary relationships amongst the vitamin K-dependent proteins and also in understanding the effect of calcium ion on the structure of protein C, Factor X, prothrombin, Factor VII and possibly other related proteins. (Supported by NIH grant MHLBI HL35058)

scholarly journals Discrimination of normal and abnormal prothrombin and protein C in plasma using a calcium ion-inhibited monoclonal antibody to a common epitope on several vitamin K-dependent proteins

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2418-2425
Author(s):  
WR Church ◽  
FH Bhushan ◽  
KG Mann ◽  
EG Bovill
Keyword(s):  
Monoclonal Antibody ◽  
Vitamin K ◽  
Calcium Ion ◽  
Metal Ion ◽  
Protein C ◽  
Conformational Transition ◽  
Vitamin K Antagonists ◽  
Antigenic Site ◽  
Divalent Metal ◽  
Carboxyglutamic Acid

Vitamin K deficiency or administration of vitamin K antagonists results in the biosynthesis of abnormal des-gamma-carboxy forms of the vitamin K-dependent proteins. Monoclonal antibody H-11 binds several vitamin K- dependent proteins at a determinant that includes the first two residues of gamma-carboxyglutamic acid. Antibody H-11 binds fully carboxylated prothrombin and protein C in the presence of EDTA but binding is inhibited by the divalent metal ions, calcium, magnesium, and manganese. By contrast, des-gamma-carboxy prothrombin and protein C bind antibody H-11 the same in the presence of EDTA or calcium ion. Antibody H-11 thus appears to bind a conserved antigenic site containing gamma-carboxyglutamic acid that in the presence of divalent metal ion undergoes a conformational transition. This ability of antibody H-11 to bind des-gamma-carboxy prothrombin and protein C in the presence of calcium ion allowed the development of an immunoassay for these proteins in plasma. Prothrombin and protein C from stably anticoagulated individuals receiving warfarin were characterized by their ability to bind antibody H-11 in the presence of calcium ion. Binding of prothrombin and protein C to antibody H-11 in the presence of calcium correlated temporally with warfarin administration. The inability of calcium ion to inhibit binding of antibody H-11 to abnormal prothrombin and protein C in plasma suggests that the circulating forms of both proteins following warfarin administration cannot undergo the metal ion-dependent conformational transition that includes sequence residues 1 through 12.

scholarly journals Nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread

2006 ◽  
Vol 203 (8) ◽  
pp. 2033-2042 ◽  
Author(s):  
Lars Hangartner ◽  
Raphaël M. Zellweger ◽  
Mattia Giobbi ◽  
Jacqueline Weber ◽  
Bruno Eschli ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cytotoxic T Lymphocyte ◽  
Antigenic Site ◽  
Neutralizing Antibody ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Antibody Binding ◽  
Surface Glycoprotein ◽  
Dependent Manner ◽  
Viral Spread

The biological relevance of nonneutralizing antibodies elicited early after infection with noncytopathic persistence-prone viruses is unclear. We demonstrate that cytotoxic T lymphocyte–deficient TgH(KL25) mice, which are transgenic for the heavy chain of the lymphocytic choriomeningitis virus (LCMV)–neutralizing monoclonal antibody KL25, mount a focused neutralizing antibody response following LCMV infection, and that this results in the emergence of neutralization escape virus variants. Further investigation revealed that some of the escape variants that arose early after infection could still bind to the selecting antibody. In contrast, no antibody binding could be detected for late isolates, indicating that binding, but nonneutralizing, antibodies exerted a selective pressure on the virus. Infection of naive TgH(KL25) mice with distinct escape viruses differing in their antibody-binding properties revealed that nonneutralizing antibodies accelerated clearance of antibody-binding virus variants in a partly complement-dependent manner. Virus variants that did not bind antibodies were not affected. We therefore conclude that nonneutralizing antibodies binding to the same antigenic site as neutralizing antibodies are biologically relevant by limiting early viral spread.

Structural organization of escherichia coli ribosomes as determined by immuno electron microscopy

1978 ◽  
Vol 36 (2) ◽  
pp. 166-167 ◽  
Author(s):  
G. Stöffler ◽  
R.W. Bald ◽  
J. Dieckhoff ◽  
H. Eckhard ◽  
R. Lührmann ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Escherichia Coli ◽  
Ribosomal Proteins ◽  
Structural Organization ◽  
Three Dimensional ◽  
Ribosomal Subunit ◽  
Spatial Arrangement ◽  
Small Subunit ◽  
Antibody Binding ◽  
Immuno Electron Microscopy

A central step towards an understanding of the structure and function of the Escherichia coli ribosome, a large multicomponent assembly, is the elucidation of the spatial arrangement of its 54 proteins and its three rRNA molecules. The structural organization of ribosomal components has been investigated by a number of experimental approaches. Specific antibodies directed against each of the 54 ribosomal proteins of Escherichia coli have been performed to examine antibody-subunit complexes by electron microscopy. The position of the bound antibody, specific for a particular protein, can be determined; it indicates the location of the corresponding protein on the ribosomal surface.The three-dimensional distribution of each of the 21 small subunit proteins on the ribosomal surface has been determined by immuno electron microscopy: the 21 proteins have been found exposed with altogether 43 antibody binding sites. Each one of 12 proteins showed antibody binding at remote positions on the subunit surface, indicating highly extended conformations of the proteins concerned within the 30S ribosomal subunit; the remaining proteins are, however, not necessarily globular in shape (Fig. 1).

HREM Study of electron-induced surface radiation damage in ReO3

1991 ◽  
Vol 49 ◽  
pp. 636-637
Author(s):  
R. Ai ◽  
H.-J. Fan ◽  
L. D. Marks
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Metal Oxides ◽  
Electron Irradiation ◽  
Transition Metal Oxides ◽  
Carbon Film ◽  
Transition Metal Ions ◽  
Surface Radiation ◽  
Valence Transition ◽  
Electron Microscopes

It has been known for a long time that electron irradiation induces damage in maximal valence transition metal oxides such as TiO2, V2O5, and WO3, of which transition metal ions have an empty d-shell. This type of damage is excited by electronic transition and can be explained by the Knoteck-Feibelman mechanism (K-F mechanism). Although the K-F mechanism predicts that no damage should occur in transition metal oxides of which the transition metal ions have a partially filled d-shell, namely submaximal valence transition metal oxides, our recent study on ReO3 shows that submaximal valence transition metal oxides undergo damage during electron irradiation.ReO3 has a nearly cubic structure and contains a single unit in its cell: a = 3.73 Å, and α = 89°34'. TEM specimens were prepared by depositing dry powders onto a holey carbon film supported on a copper grid. Specimens were examined in Hitachi H-9000 and UHV H-9000 electron microscopes both operated at 300 keV accelerating voltage. The electron beam flux was maintained at about 10 A/cm2 during the observation.

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