Novel high-affinity binders of human interferon gamma derived from albumin-binding domain of protein G
Jawid N. Ahmad
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Jawid N. Ahmad and Jingjing Li contributed equally to this work.
Search for more papers by this authorJingjing Li
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Jawid N. Ahmad and Jingjing Li contributed equally to this work.
Search for more papers by this authorLada Biedermannová
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorMilan Kuchař
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorHana Šípová
Institute of Photonics and Electronics of the ASCR, v. v. i., Chaberská 57, 182 51 Prague, Czech Republic
Search for more papers by this authorAlena Semerádtová
Faculty of Science, Jan Evangelista Purkyně University, České Mládeže 8, 400 96 Ústí nad Labem, Czech Republic
Search for more papers by this authorJiří Černý
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorHana Petroková
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorPavel Mikulecký
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorJiří Polínek
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorOndřej Staněk
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorJiří Vondrášek
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorJiří Homola
Institute of Photonics and Electronics of the ASCR, v. v. i., Chaberská 57, 182 51 Prague, Czech Republic
Search for more papers by this authorJan Malý
Faculty of Science, Jan Evangelista Purkyně University, České Mládeže 8, 400 96 Ústí nad Labem, Czech Republic
Search for more papers by this authorRadim Osička
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorPeter Šebo
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorCorresponding Author
Petr Malý
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Praha 4, Czech Republic===Search for more papers by this authorJawid N. Ahmad
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Jawid N. Ahmad and Jingjing Li contributed equally to this work.
Search for more papers by this authorJingjing Li
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Jawid N. Ahmad and Jingjing Li contributed equally to this work.
Search for more papers by this authorLada Biedermannová
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorMilan Kuchař
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorHana Šípová
Institute of Photonics and Electronics of the ASCR, v. v. i., Chaberská 57, 182 51 Prague, Czech Republic
Search for more papers by this authorAlena Semerádtová
Faculty of Science, Jan Evangelista Purkyně University, České Mládeže 8, 400 96 Ústí nad Labem, Czech Republic
Search for more papers by this authorJiří Černý
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorHana Petroková
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorPavel Mikulecký
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorJiří Polínek
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorOndřej Staněk
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorJiří Vondrášek
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorJiří Homola
Institute of Photonics and Electronics of the ASCR, v. v. i., Chaberská 57, 182 51 Prague, Czech Republic
Search for more papers by this authorJan Malý
Faculty of Science, Jan Evangelista Purkyně University, České Mládeže 8, 400 96 Ústí nad Labem, Czech Republic
Search for more papers by this authorRadim Osička
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorPeter Šebo
Institute of Microbiology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Search for more papers by this authorCorresponding Author
Petr Malý
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague, Czech Republic
Institute of Biotechnology of the ASCR, v. v. i., Vídeňská 1083, 142 20 Praha 4, Czech Republic===Search for more papers by this authorAbstract
Recombinant ligands derived from small protein scaffolds show promise as robust research and diagnostic reagents and next generation protein therapeutics. Here, we derived high-affinity binders of human interferon gamma (hIFNγ) from the three helix bundle scaffold of the albumin-binding domain (ABD) of protein G from Streptococcus G148. Computational interaction energy mapping, solvent accessibility assessment, and in silico alanine scanning identified 11 residues from the albumin-binding surface of ABD as suitable for randomization. A corresponding combinatorial ABD scaffold library was synthesized and screened for hIFNγ binders using in vitro ribosome display selection, to yield recombinant ligands that exhibited Kd values for hIFNγ from 0.2 to 10 nM. Molecular modeling, computational docking onto hIFNγ, and in vitro competition for hIFNγ binding revealed that four of the best ABD-derived ligands shared a common binding surface on hIFNγ, which differed from the site of human IFNγ receptor 1 binding. Thus, these hIFNγ ligands provide a proof of concept for design of novel recombinant binding proteins derived from the ABD scaffold. Proteins 2011. © 2012 Wiley Periodicals, Inc.
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