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SHR Neuro Krebs Kardio Lipid

Chromikova, V; Mader, A; Hofbauer, S; Göbl, C; Madl, T; Gach, JS; Bauernfried, S; Furtmüller, PG; Forthal, DN; Mach, L; Obinger, C; Kunert, R.
Introduction of germline residues improves the stability of anti-HIV mAb 2G12-IgM.
Biochim Biophys Acta. 2015; 1854(10 Pt A):1536-1544 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Madl Tobias
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Number of Figures: 7
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Abstract:
Immunoglobulins M (IgMs) are gaining increasing attention as biopharmaceuticals since their multivalent mode of binding can give rise to high avidity. Furthermore, IgMs are potent activators of the complement system. However, they are frequently difficult to express recombinantly and can suffer from low conformational stability. Here, the broadly neutralizing anti-HIV-1 antibody 2G12 was class-switched to IgM and then further engineered by introduction of 17 germline residues. The impact of these changes on the structure and conformational stability of the antibody was then assessed using a range of biophysical techniques. We also investigated the effects of the class switch and germline substitutions on the ligand-binding properties of 2G12 and its capacity for HIV-1 neutralization. Our results demonstrate that the introduced germline residues improve the conformational and thermal stability of 2G12-IgM without altering its overall shape and ligand-binding properties. Interestingly, the engineered protein was found to exhibit much lower neutralization potency than its wild-type counterpart, indicating that potent antigen recognition is not solely responsible for IgM-mediated HIV-1 inactivation. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Amino Acid Substitution -
Animals -
Antibodies, Monoclonal - biosynthesis
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - pharmacology
Base Sequence -
CHO Cells -
Cricetulus -
Gene Expression -
HEK293 Cells -
HIV Antibodies - biosynthesis
HIV Antibodies - chemistry
HIV Antibodies - immunology
HIV Antibodies - pharmacology
HIV Envelope Protein gp120 - antagonists & inhibitors
HIV Envelope Protein gp120 - chemistry
HIV Envelope Protein gp120 - immunology
HIV-1 - drug effects
HIV-1 - growth & development
Humans -
Immunoglobulin Class Switching - genetics
Immunoglobulin M - biosynthesis
Immunoglobulin M - chemistry
Immunoglobulin M - immunology
Immunoglobulin M - pharmacology
Molecular Sequence Data -
Mutation -
Neutralization Tests -
Protein Conformation -
Protein Engineering -
Protein Stability -
Recombinant Proteins - biosynthesis
Recombinant Proteins - chemistry
Recombinant Proteins - immunology
Recombinant Proteins - pharmacology
Sequence Alignment -
Structure-Activity Relationship -

Find related publications in this database (Keywords)
Antibody engineering
Germline
HIV
IgM
Protein stability
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