PuSH - Publikationsserver des Helmholtz Zentrums München

Chromikova, V.* ; Mader, A.* ; Hofbauer, S.* ; Göbl, C. ; Madl, T. ; Gach, J.S.* ; Bauernfried, S.* ; Furtmüller, P.G.* ; Forthal, D.N.* ; Mach, L.* ; Obinger, C.* ; Kunert, R.*

Introduction of germline residues improves the stability of anti-HIV mAb 2G12-IgM.

Biochim. Biophys. Acta-Proteins Proteom. 1854, 1536–1544 (2015)
Verlagsversion DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hiv ; Igm ; Antibody Engineering ; Germline ; Protein Stability
ISSN (print) / ISBN 1570-9639
e-ISSN 1878-1454
Quellenangaben Band: 1854, Heft: 10, Seiten: 1536–1544 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed