Protein Shape Effects
Protein−protein interactions are usually studied in dilute buffered solutions with macromolecule concentrations of <10 g/L. In cells, however, the macromolecule concentration can exceed 300 g/L, resulting in nonspecific interactions between macromolecules. These interactions can be divided into hard-core steric repulsions and "soft" chemical interactions.
In work published in PNAS, researchers in the Pielak Group, collaborating with researchers from the Department of Biochemistry & Biophysics, Lineberger Comprehensive Cancer Center, and the Integrative Program for Biological and Genome Sciences, all here at UNC, test a hypothesis from scaled particle theory; the influence of hard-core repulsions on a protein dimer depends on its shape.
Lab members tested the idea using a side-by-side dumbbell-shaped dimer and a domain-swapped ellipsoidal dimer. Both dimers are variants of the B1 domain of protein G and differ by only three residues. The results from the relatively inert synthetic polymer crowding molecules, Ficoll and PEG, support the hypothesis, indicating that the domain-swapped dimer is stabilized by hard-core repulsions while the side-by-side dimer shows little to no stabilization.
Members of the Pielak Group also show that protein cosolutes, which interact primarily through nonspecific chemical interactions, have the same small effect on both dimers. Their results suggest that the shape of the protein dimer determines the influence of hard-core repulsions, providing cells with a mechanism for regulating protein−protein interactions.