Constructing protein polyhedra via orthogonal chemical interactions

Abstract

A large fraction of proteins naturally exist as symmetrical homooligomers or homopolymers 1. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design 2-5. As synthesized by ribosomes, proteins are inherently asymmetric. Thus, they must acquire multiple surface patches that selectively associate to generate different symmetry elements needed to form higher-order architectures 1,6-a daunting task for protein design. Here we introduce an inorganic chemical approach to address this outstanding problem, whereby multiple modes of protein-protein interactions and symmetry are simultaneously achieved by selective, "one-pot" coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and Zn-binding motifs assembles through concurrent Fe 3+ and Zn 2+ coordination into discrete dodecameric and hexameric cages. Closely resembling natural polyhedral protein architectures 7,8 and unique among designed systems 9-13 , our artificial cages possess tightly packed shells devoid of large apertures, yet they can assemble and disassemble in response to diverse stimuli owing to their heterobimetallic construction on minimal interproteinbonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomer] to [8 Fe:21 Zn:12 protomer], these protein cages represent some of the compositionally most complex protein assemblies-or inorganic coordination complexes-obtained by design. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Two-tier supramolecular encapsulation of small molecules in a protein cage

“…De novo design has provided access to an array of novel protein assemblies by traversing unexplored sequence, structure, and fitness landscapes 41 , 42 . Introducing other molecular building blocks to designed assemblies increases the dimensionality of this parameter space exponentially 17 , 18 , 43 – 45 . The emergent properties that result can take us one step closer to matching the structural sophistication and functional elegance that we see in nature.…”

“…Perhaps, for this reason, the incorporation of biological components beyond proteins and nucleic acids has not been extensively explored, as this requires developing an additional set of, likely harder to predict, self-assembly rules. Considering the structural and functional complexity that nature achieves through the coordinated self-assembly of diverse (macro)molecular components, expansion of protein cage engineering to include other molecular species has considerable potential to advance structural complexity and functional scope 15 – 18 .…”

Converting histidine-induced 3D protein arrays in crystals into their 3D analogues in solution by metal coordination cross-linking

“…While a variety of different dimensional protein assemblies have been reported by using different noncovalent and covalent interactions as driving forces 11,[21][22][23][24][25][26][27][28][29][30][31][32] , the majority of the designed PPIs for high ordered protein assemblies is based on single noncovalent or covalent interaction as a driving force. Here, we demonstrate that a combination of π-π interaction and metal coordination represents an effective way to build 3D protein arrays in crystals and solution.…”

“…Such naturally occurring protein assemblies have been extensively studied by synthetic biologists and chemists in the field of nanoscience for exploring biomimetic methods to prepare new nanoscale protein materials with valuable functions [13][14][15][16][17][18][19][20] . Importantly, some considerable applications of designing protein and constructing multifarious supramolecular protein material by varied strategies 11,[21][22][23][24][25][26][27][28][29][30][31][32] for scientists had been carried out to rival the size and functionality of natural protein. These engineered protein assemblies are competitive owing to their excellent potential biocompatibility and biofunctionality.…”

Porphyrin/Ionic‐Liquid Co‐assembly Polymorphism Controlled by Liquid–Liquid Phase Separation

“…Multicomponent co-assembly is ubiquitous in nature and has emerged as an effective and elegant strategy to construct multifunctional materials with increasing complexity and tunable properties. [1] For example, RNA can co-assemble with proteins and peptides to form liquid organelles through supramolecular co-assembly. [2] Additionally, multifunctional co-assemblies exhibit distinguished physicochemical properties, such as ultralong phosphorescence and improved stability compared with other assemblies, as well as unique energytransport processes.…”