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Destabilization of CH2 domains in intact IgG2 is accompanied by reduced ability to inhibit complement system factor C1

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Abstract

Fc fragments (hFc) of human myeloma IgG2 proteins LOM and SIN having core hinge (Cys-Cys-Val-Glu-Cys-Pro-Pro-Cys) were first obtained by a modified proteolytic procedure. The thermostability of CH2 domains inside of standard Fc, hFc fragments, and intact IgG2 LOM and SIN was studied by fluorescence spectroscopy. It was found that CH2 domains of intact IgG2 are destabilized. The destabilization is accompanied by reduced ability of IgG2 to inhibit the activation of complement system by classical pathway. This could be due to the decrease in the affinity of CH2 domains to factor C1q.

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Abbreviations

DSS:

disuccinimidyl suberate

FITC:

fluorescein isothiocyanate

Fv-subfragment:

structure formed by pair of variable domains VL-VH

ΔGst :

Gibbs free energy of CH2 domain stabilization

H(L) chains:

heavy (light) chains

IgG:

immunoglobulins of G class

Tm, ΔHm, ΔSm :

melting temperature, enthalpy, and entropy of CH2 domain, respectively

VH :

variable domains of heavy chain

VL :

variable domains of light chain

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya ul. 3, 142290, Pushchino, Moscow Region, Russia

    M. A. Timchenko & V. M. Tischenko

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  1. M. A. Timchenko
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Correspondence to V. M. Tischenko.

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Published in Russian in Biokhimiya, 2013, Vol. 78, No. 6, pp. 859–866.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM13-018, April 14, 2013.

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Timchenko, M.A., Tischenko, V.M. Destabilization of CH2 domains in intact IgG2 is accompanied by reduced ability to inhibit complement system factor C1. Biochemistry Moscow 78, 667–673 (2013). https://doi.org/10.1134/S0006297913060126

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  • DOI: https://doi.org/10.1134/S0006297913060126

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