Redox- and metal-directed structural diversification in designed metalloprotein assemblies

Abstract

Herein we describe a designed protein building block whose self-assembly behaviour is dually gated by the redox state of disulphide bonds and the identity of exogenous metal ions. This protein...

Heme-substituted protein assembly bridged by synthetic porphyrin: achieving controlled configuration while maintaining rotational freedom

“…The introduction of dened exibility into articial protein assemblies could allow control of their motion, thereby providing them with motion-based functions, leading to the development of dynamic articial protein assemblies, a eld that currently has only limited examples. 7,36,37…”

Atomically Accurate Design of Metalloproteins with Predefined Coordination Geometries

“…To date, most de novo -designed metalloproteins have been based on α-helical motifs. ,− The small sizes and highly parametrizable nature of these systems have facilitated the incorporation of metal ions with desired coordination environments and proved invaluable in exploring the minimal structural requirements in proteins for metal-based functions. ,,− Yet, the same features also restrict the scope of metal active sites and geometries that can be accommodated as well as the incorporation of functionally important structural motifs (e.g., large cavities, flexible loops). Similar challenges also apply to non-α-helical peptide motifs. − Examples of larger designed metalloproteins have either entailed coordinatively saturated metal centers, resulted in unexpected deviations from targeted coordination geometries, − or relied on recreating secondary structure elements adopted from natural metalloproteins. , We developed an alternative design approach, Metal-Templated Interface Redesign, based on the metal-directed self-assembly of protein building blocks into oligomeric architectures. − Using the structures of these assemblies as a template, the protein–protein interfaces bearing the nucleating metal centers are engineered to increase preorganization for metal binding and obtain diverse metal-based functions. ,− However, the structural outcome of metal-directed protein assembly is not always predictable, and the resulting interfacial metal centers are generallybut not alwayscoordinatively saturated, limiting access to alternative coordination geometries of interest. ,, …”