0000000000236095
AUTHOR
Björn Nilsson
High-resolution solution NMR structure of the Z domain of staphylococcal protein A
Staphylococcal protein A (SpA) is a cell-wall-bound pathogenicity factor from the bacterium Staphylococcus aureus. Because of their small size and immunoglobulin (IgG)-binding activities, domains of protein A are targets for protein engineering efforts and for the development of computational approaches for de novo protein folding. The NMR solution structure of an engineered IgG-binding domain of SpA, the Z domain (an analog of the B domain of SpA), has been determined by simulated annealing with restrained molecular dynamics on the basis of 671 conformational constraints. The Z domain contains three well-defined alpha-helices corresponding to polypeptide segments Lys7 to Leu17 (helix 1), G…
The mechanism of binding staphylococcal protein A to immunoglobin G does not involve helix unwinding.
Structural changes in staphylococcal protein A (SpA) upon its binding to the constant region (Fc) of immunoglobulin G (IgG) have been studied by nuclear magnetic resonance and circular dichroism (CD) spectroscopy. The NMR solution structure of the engineered IgG-binding domain of SpA, the Z domain (an analogue of the B domain of SpA), has been determined by simulated annealing with molecular dynamics, using 599 distance and dihedral angle constraints. Domain Z contains three alpha-helices in the polypeptide segments Lys7 to His18 (helix 1), Glu25 to Asp36 (helix 2), and Ser41 to Ala54 (helix 3). The overall chain fold is an antiparallel three-helical bundle. This is in contrast to the previ…
High Resolution Solution NMR Structure of the Z Domain of Staphylococcal Protein A. Analysis of Secondary Structure for Free Z Domain and Bounded to IgG Antibody
Staphylococcal protein A (SpA) is a cell-wall-bound pathogenicity factor from the bacterium Staphylcoccus aureus. It exhibits tight binding to many IgG, IgA and IgM molecules at site(s) different from antigen-combining site. Because of their small size and immunoglobulin (IgG)-binding activities, domains of protein A are important targets for protein engineering efforts and for the development of computational approaches for de novo protein folding.