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001-es BibID:	BIBFORM131622
035-os BibID:	(scopus)105011746733
Első szerző:	Hajdu Tímea (biomérnök)
Cím:	Fluorescence labeling-induced structural rearrangement of a monoclonal IgG revealed by biophysical experiments and simulations / Hajdu Tímea, Rebenku István, Cano Tayde Gabriela Serrano, Mocsár Gábor, Bécsi Bálint, Erdődi Ferenc, Nagy Peter
Dátum:	2025
ISSN:	0141-8130
Megjegyzések:	Although it is known that labeling antibodies with fluorescent dyes impairs their function, the underlying mechanism remains unclear. In this study, we show that multiple antibody functions decline in a strikingly similar way as the degree of labeling increases, suggesting that labeling induces a global structural change affecting the entire IgG molecule. Fluorescence anisotropy decay experiments revealed faster nanosecond-scale dynamics in labeled antibodies. FRET measurements showed that the Fc region moves closer to the hypervariable region upon labeling, further indicating major structural rearrangements. Molecular dynamics simulations confirmed that labeled antibodies adopt a more compact structure, bringing the Fc and Fab regions closer together. During simulations, the dye molecules gradually became less exposed to solvent, implicating the hydrophobic effect as a driver of structural collapse. The reduced antigen-binding affinity caused by labeling was partially restored by glycerol, likely due to its ability to weaken hydrophobic interactions. Together, these findings provide molecular-level insight into how fluorescent labeling disrupts antibody structure and function.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Fluoreszcens jelölés IgG struktúra és dinamika hidrofób effektus
Megjelenés:	International Journal Of Biological Macromolecules. - 321 (2025), p. 1-45. -
További szerzők:	Rebenku István (1990-) (molekuláris biológus) Serrano Cano, Tayde Gabriela (1993-) (molekuláris biológus) Mocsár Gábor (1981-) (biofizikus) Bécsi Bálint (1981-) (vegyészmérnök) Erdődi Ferenc (1953-) (biokémikus) Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:	Ann133421 OTKA K138075 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM087409
Első szerző:	Hajdu Tímea (biomérnök)
Cím:	Comprehensive Model for Epidermal Growth Factor Receptor Ligand Binding Involving Conformational States of the Extracellular and the Kinase Domains / Tímea Hajdu, Tímea Váradi, István Rebenku, Tamás Kovács, János Szöllösi, Péter Nagy
Dátum:	2020
ISSN:	2296-634X
Megjegyzések:	The epidermal growth factor (EGF) receptor (EGFR) undergoes ligand-dependent dimerization to initiate transmembrane signaling. Although crystallographic structures of the extracellular and kinase domains are available, ligand binding has not been quantitatively analyzed taking the influence of both domains into account. Here, we developed a model explicitly accounting for conformational changes of the kinase and extracellular domains, their dimerizations and ligand binding to monomeric and dimeric receptor species. The model was fitted to ligand binding data of suspended cells expressing receptors with active or inactive kinase conformations. Receptor dimers with inactive, symmetric configuration of the kinase domains exhibit positive cooperativity and very weak binding affinity for the first ligand, whereas dimers with active, asymmetric kinase dimers are characterized by negative cooperativity and subnanomolar binding affinity for the first ligand. The homodimerization propensity of EGFR monomers with active kinase domains is _100-times higher than that of dimers with inactive kinase domains. Despite this fact, constitutive, ligand-independent dimers are mainly generated from monomers with inactive kinase domains due to the excess of such monomers in the membrane. The experimental finding of increased positive cooperativity at high expression levels of EGFR was recapitulated by the model. Quantitative prediction of ligand binding to different receptor species revealed that EGF binds to receptor monomers and dimers in an expression-level dependent manner without significant recruitment of monomers to dimers upon EGF stimulation below the phase transition temperature of the membrane. Results of the fitting offer unique insight into the workings of the EGFR.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk EGF EGFR
Megjelenés:	Frontiers in Cell and Developmental Biology. - 8 (2020), p. 1-53. -
További szerzők:	Váradi Tímea (1973-) (biológus) Rebenku István (1990-) (molekuláris biológus) Kovács Tamás (1985-) (általános orvos) Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00020 GINOP GINOP-2.2.1-15-2017-00044 GINOP NKFIH K120302 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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