Structural Insight into Binary Protein Metal–Organic Frameworks with Ferritin Nanocages as Linkers and Nickel Clusters as Nodes

Abstract

Metal–organic frameworks (MOFs) hold great promise for numerous applications. However, proteins, carriers of biological functions in living systems, have not yet been fully explored as building blocks for the construction of MOFs. This work presents a strategy for the fabrication of binary MOFs. Considering octahedral ferritin symmetry, four His2 (His–His) motifs were first incorporated into the exterior surface of a ferritin nanocage near each C4 channel, yielding protein linkers with multiple metal‐binding sites (bisH‐SF). Secondly, by adding nickel ions to bisH‐SF solutions triggers the self‐assembly of ferritin nanocages into a porous 3D crystalline MOF with designed protein lattice, where two adjacent ferritin molecules along the C4 symmetry axes are bridged by four dinuclear or tetranuclear nickel clusters depending on Ni2+ concentration. This work provides a simple approach for precise control over a binary protein–metal crystalline framework, and the resulting MOFs exhibited inherent ferroxidase activity and peroxidase‐like catalytic activity.

Protein interface redesign facilitates the transformation of nanocage building blocks to 1D and 2D nanomaterials

“…Nowadays, scientists are able to accurately control the protein self-assembly behaviors to construct various supramolecular structures through the rational design of PPIs. Though a variety of intricate protein nanostructures such as hollow protein cages, filaments/tubules, nanosheets, and 3D crystalline frameworks have been created [18][19][20][21][22][23][24][36][37][38][39][40][41] , rendering directed assembly of protein-building blocks into the customtailored nanoarchitectures remains challenging. Our reported protein engineering approach could tune the inherent head-toside interaction manner of two adjacent dimeric protein-building blocks to the fully or partially side-by-side manner by redesigning protein interfaces, yielding directed assembly of the building blocks, thereby facilitating the self-assembly transformation of the dimeric building blocks from hollow protein nanocage into 1D or 2D nanomaterials.…”

“…It is well known that protein-protein interactions (PPIs) at protein interfaces are the chief contributors to construct the diversified protein nanostructures [11][12][13] . Following Nature's inspiration to assemble protein building blocks into exquisite nanostructures, various self-assembly strategies, such as symmetry-directed design [14][15][16][17] , metal coordination 7,[18][19][20] , host-guest interactions 21,22 , and the use of bifunctional ligands 23,24 , have been applied to construct 1D, 2D, and 3D hierarchical protein nanostructures. Among these various protein nanostructures, natural protein nanocages represent a class of versatile nanomaterials that fulfill a wide range of functions, such as CO 2 fixation by carboxysomes 25 , iron metabolism by ferritins 26 , DNA protection by Dps 27 , and nucleic acid storage and transport by viral capsids 28 .…”

Protein interface redesign facilitates conversion of zero-dimensional protein nanomaterials to their one- and two-dimensional analogues

“…Nowadays, scientists are able to accurately control over the protein self-assembly behaviors to construct multifarious supramolecular structures through rational design of PPIs. Though a variety of intricate protein nanostructures such as 0D polyhedral cages, 1D laments/tubules, 2D nanosheets, and 3D crystalline frameworks have been created [18][19][20][21][22][23][35][36][37][38][39][40] , rendering directed assembly of protein building blocks into the custom-tailored nanoarchitectures remains challenging. Our reported protein engineering approach could tune the inherent head-to-side interaction manner of two adjacent dimeric protein building blocks to the fully or partially side-by-side manner by designing new protein interfaces, yielding directed assembly of the building blocks, thereby facilitating conversion of 0D protein nanocage into 1D or 2D nanomaterials.…”

“…It is well-known that protein-protein interactions (PPIs) at protein interfaces are the chief contributors to construct the diversi ed protein nanostructures [11][12][13] . Following Nature's inspiration to assemble protein building blocks into exquisite nanostructures, various self-assembly strategies, such as symmetry-directed design [14][15][16][17] , metal-coordination 7,18,19 , host-guest interactions 20,21 and the use of bifunctional ligands 22,23 have been applied mainly to construct one-, two-and threedimensional hierarchical protein nanostructures. In contrast to the above 1D, 2D and 3D protein architectures, Nature has also evolved a series of protein nanocages to ful ll a wide range of functions such as CO 2 xation by carboxysomes 24 , iron metabolism by ferritin 25 , DNA protection by Dps 26 , and nucleic acid storage and transport by viral capsids 27 .…”

Protein cages as building blocks for superstructures

“…The alternation of the 2D and 3D structures could be controlled by adjusting the pH or the reaction time. To acquire metal-ligand coordination with nickel ions as the driving force, Gu et al linked His 2 motifs to Thr157 close to the C4 axes of ferritins, resulting in the successful generation of a binary protein-metal crystalline framework [22].…”