Investigation of the cooperative structure of Fc fragments from myeloma immunoglobulin G

Biochemistry
V M TischenkoV P Zav'yalov

Abstract

The cooperative structure of Fc fragments prepared from myeloma human IgG1 was studied using scanning microcalorimetry and fluorescence at pH 4.2-8.0. It was shown that the first to be melted are CH2 domains whose interaction with each other is rather weak, while that with CH3 domains is strong. Then CH3 domains which form a single cooperative block are melted. The data for the structure of the Fc fragment in solution agree with the X-ray data according to which the interaction between CH2 domains is mediated by the carbohydrate moiety while the two CH3 domains are strongly associated. The presence of intensive CH2-CH3 interaction is a distinctive feature of the state of the Fc fragment in the given pH region as compared to that at pH <4.1 [Tischenko, V. M., et al. (1982) Eur. J. Biochem. 126, 517-521; Ryazantsev, S., et al. (1990) Eur. J. Biochem. 190, 393-399]. First, cis interactions greatly increase the free energy of the native structure stabilization in CH2 domains. Second, they decrease this energy for CH3 domains when compared to the state of the latter at pH 3.8 or within the Fc' fragment (the dimer of CH3 domains). The temperature and enthalpy of melting of CH2 domains coincide in all the samples studied despite heter...Continue Reading

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Citations

Dec 24, 2008·Pharmaceutical Research·R Matthew FesinmeyerYatin R Gokarn
Nov 5, 2002·Immunology Letters·Vladimir M Tischenko, Vladimir P Zav'yalov
Apr 23, 2003·Immunology Letters·Vladimir M Tischenko, Vladimir P Zav'yalov
Nov 13, 2003·Immunology Letters·Vladimir M TischenkoVladimir P Zav'yalov
Jun 1, 1995·Trends in Microbiology·G Sczakiel, W Nedbal
Jul 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Naresh ChennamsettyBernhardt L Trout
May 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Peter SondermannJeffrey V Ravetch
Dec 26, 2012·Protein Engineering, Design & Selection : PEDS·Michael W TraxlmayrChristian Obinger
Apr 2, 2009·Molekuliarnaia biologiia·V M TishchenkoO P Blizniukov
Jun 14, 2013·PloS One·Sergey RyazantsevVladimir Zav'yalov
Dec 22, 2012·Molecular Pharmaceutics·Jian Zhang-van EnkJifeng Zhang
Feb 18, 2014·FEBS Letters·Haixia WuChristopher J Roberts
Nov 28, 2013·Journal of Pharmaceutical Sciences·Martin S NeergaardMarco Van De Weert
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