De novo Designed Bacteriochlorophyll-Binding Helix-Bundle Proteins

The construction of small synthetic proteins that bind only one or a small number of (bacterio)chlorophylls ((B)Chls) is a powerful approach to understand the concepts and guidelines of protein-(B)Chl interactions and assembly; the systems can be extended, in a stepwise fashion, by adding other cofactors or by oligomerization. We review the unique aspects of the de novo design and construction of (B)Chl-binding proteins, and describe recent progress and challenges in designing new BChl-protein platforms for delineating general rules and guidelines of (B)Chl-protein assembly, structure, and function. The relevant aspects of chlorophyll (Chl) and BChl chemical structures are outlined, as well as the modes of interactions with natural proteins. Two distinct strategies are then described for designing de novo water-soluble (B)Chl-binding proteins. The first strategy is based on the covalent assembly of modular four-helix bundle proteins, the second follows the original non-covalent heme-binding protein maquette design, which relies on self-assembly of amphiphilic helices that is primarily driven by the hydrophobic effect. Finally, we demonstrate the extension of the latter to designing transmembrane-like versions of (B)Chl-protein maquettes.