Zinc clasp-based reversible toolset for selective metal-mediated protein heterodimerization

Abstract

Considering the complex biological quandaries of the tightly woven networks of biological macromolecules, we present an optimized zinc clasp-based toolset from the CD4 co-receptor and Lck protein tyrosine kinase complex for selective, tight and fully reversible protein heterodimerization (log K₁₂ = 18.6). We demonstrated its utility on CD4-tagged proteins with capture from bacterial lysate and constructed molecular baits using a new small-molecule tether.