Cocrystallization of an immunoglobulin light chain dimer with bis(dinitrophenyl) lysine: tandem binding of two ligands, one with and one without accompanying conformational changes in the protein

Molecular Immunology
A B EdmundsonJ N Herron

Abstract

Previous studies showed that the Mcg dimer of immunoglobulin light chains bound bis(dinitrophenyl)lysine both in trigonal crystals and in solution. On prolonged storage in ammonium sulfate, mixtures of ligand and protein produced small trigonal cocrystals in low frequency. These crystals were nearly isomorphous with those of the unliganded dimer in which the subunits were covalently linked by an interchain disulfide bond. By difference Fourier analyses at 3.5 A resolution and subsequent crystallographic refinement, the cocrystals were found to contain molecules with two ligands aligned in tandem along the interface of the variable (V) domains of the protein. One ligand molecule adopted an almost fully extended conformation, with the epsilon-DNP ring situated near the floor, the alpha-carboxyl group directed toward the solvent at the entry, and the alpha-DNP ring outside the rim of the main cavity. As if architecturally designed, the ligand was located symmetrically between the two domains in an orientation that was compatible with both the unaltered structure of the cavity lining and with the known crystal packing interactions of neighboring protein molecules. The second ligand molecule in the cocrystal lodged in the deep pocke...Continue Reading

References

Nov 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·R ZidovetskiI Pecht
Sep 24, 1974·Biochemistry·J W Fett, H F Deutsch
Nov 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·D M SegalD R Davies
Dec 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·S RudikoffD R Davies
May 9, 1972·Biochemistry·A B EdmundsonM K Wood
Dec 17, 1965·Science·O Smithies

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Citations

Jan 1, 1994·Research in Immunology·A B EdmundsonB L Hanson
Aug 9, 2018·Chemical Communications : Chem Comm·Luis M Blancas-MejiaMarina Ramirez-Alvarado
Jul 1, 1993·Proteins·A B EdmundsonH M Geysen
Jan 1, 1997·Indian Journal of Pediatrics·M P Desai

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