Metal-Directed Protein Self Assembly
By E. N. Salgado, R. Radford, F. Tezcan. 2010
262 citations recorded by the source corpus.
CONSPECTUS Proteins are Nature’s premier building blocks for constructing sophisticated nanoscale architectures that carry out complex tasks and chemical transformations. It is estimated that 70–80% of all proteins are permanently oligomeric, that is, they are composed of multiple proteins that are held together in precise spatial organization through non-covalent interactions. While it is of great fundamental interest to understand the physicochemical basis of protein self-assembly, the mastery of protein-protein interactions (PPIs) would also allow access to novel biomaterials using Nature’s favorite and most versatile building block. With this possibility in mind, we have developed a new approach, Metal Directed Protein Self-Assembly (MDPSA), which utilizes the strength, directionality and selectivity of metal-ligand interactions to control PPIs. At its core, MDPSA is inspired by supramolecular coordination chemistry which exploits metal coordination for the self-assembly of small molecules into discrete, more-or-less predictable higher-order structures. Proteins, however, are not exactly small molecules or simple metal ligands: they feature extensive, heterogeneous surfaces that can interact with each other and with metal ions in unpredictable ways. We will start this Account by first describing the challenges of using entire proteins as molecular building blocks. This will be followed by our work on a model protein (cytochrome cb562) to both highlight and overcome those challenges toward establishing some ground rules for MDPSA. Proteins are also Nature’s metal ligands of choice. In MDPSA, once metal ions guide proteins into forming large assemblies, they are by definition embedded within extensive interfaces formed between protein surfaces. These complex surfaces make an inorganic chemist’s life somewhat difficult, yet they also provide a wide platform to modulate the metal coordination environment through distant, non-covalent interactions – exactly as natural metalloproteins and enzymes do. We will describe our computational and experimental efforts on restructuring the non-covalent interaction network formed between proteins surrounding the interfacial metal centers. This approach of metal templating followed by the redesign of protein interfaces (Metal-Templated Interface Redesign, MeTIR) not only provides a route to engineer de novo PPIs and novel metal coordination environments, but also carries possible parallels to the evolution of metalloproteins.
Subfields: Materials Chemistry, Molecular Biology, Physical and Theoretical Chemistry
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Citations in the corpus
- Metal-directed, chemically-tunable assembly of one-, two- and three-dimensional crystalline protein arrays (2012, unknown): “Previously, we focused on the use of the four-helix-bundle heme protein, cyt cb 562 , as a building block, because it is stable, monomeric at mM concentrations, and has a compact, cylindrical shape 22 .”
- De novo protein design, a retrospective (2020, background): “…peptides (Ghadiri and Choi, 1990; Ruan et al., 1990; Krantz and Sosnick, 2001; Tang et al., 2007; Signarvic and DeGrado, 2009) as well as Zn2+-mediated dimerization of de novo designed proteins (Handel and DeGrado, 1990; Handel et al., 1993) and natural proteins (Salgado et al., 2007, 2010).”