Allosteric regulation of C-reactive protein

Serum-soluble C-reactive protein (CRP) is a highly conserved innate immune pattern recognition molecule comprised of five identical globular subunits arranged in a cyclic pentameric shape. While the interactions between each of the five subunits are noncovalent, each monomer possesses an intra-subunit disulfide bond linking adjacent β-strands within the same β-sheet (ie, a cross-strand disulfide bond). This bond is necessary for the folding and polymerization of CRP during its synthesis, but also serves as a regulator of CRP function. Reduction of the bond initiates a conformational, allosteric change that exposes a hidden binding site for cholesterol and amplifies CRP-mediated cellular responses. In this review, we discuss the folding, multimerization, and structural changes CRP undergoes during its life cycle. We also highlight the role of the cross-strand disulfide bond in CRP, both for its contributions to the assembly of the pentamer and for its role as an allosteric regulator of CRP function.