Design of metal-mediated protein assemblies via hydroxamic acid functionalities

Subramanian, Rohit H.; Bailey, J.B.; Chiong, Jerika A.; Li, Yiying; Golub, Eyal; Tezcan, F.A.

doi:10.1038/s41596-021-00535-z

Cited by 17 publications

(16 citation statements)

References 90 publications

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“…Coordination chemistry of metal ions has also been explored for the creation of controllable supramolecular complexes, including small homo-oligomers, polyhedral assemblies, and even crystals (Figure 2d). [13,[55][56][57][58][59][60][61][62] This versatile methodology can be extensively used in combination with the coiled-coil approach to mediate the self-assembly of polyhedral nanomaterials by utilising coiled-coil modules that oligomerize upon binding of divalent transition metal ions (e. g. Zn 2 + , Cu 2 + , Co 2 + , Ni 2 + ). [63] The metal coordination approach has also generated compact stimulus-responsive bimetallic protein cages (BMCs) from asymmetric monomers.…”

Section: First Principle-based Design Approachesmentioning

confidence: 99%

De Novo Design of Polyhedral Protein Assemblies: Before and After the AI Revolution

et al. 2023

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Self-assembling polyhedral protein biomaterials have gained attention as engineering targets owing to their naturally evolved sophisticated functions, ranging from protecting macromolecules from the environment to spatially controlling biochemical reactions. Precise computational design of de novo protein polyhedra is possible through two main types of approaches: methods from first principles, using physical and geometrical rules, and more recent data-driven methods based on artificial intelligence (AI), including deep learning (DL). Here, we retrospect first principle-and AI-based approaches for designing finite polyhedral protein assemblies, as well as advances in the structure prediction of such assemblies. We further highlight the possible applications of these materials and explore how the presented approaches can be combined to overcome current challenges and to advance the design of functional protein-based biomaterials.

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Section: First Principle-based Design Approachesmentioning

confidence: 99%

De Novo Design of Polyhedral Protein Assemblies: Before and After the AI Revolution

et al. 2023

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“…, histidine) to ionization can be exploited at a protein–protein interface, with the repulsion of like-charges promoting disassembly. Several studies have demonstrated systems to respond to acidification, mimicking certain viral capsids. , Other studies have exploited disulfide bonds to chemically link protein subunits, conferring stability in oxidizing environments outside the cell but not in intracellular environments, which are typically reducing. − Similarly, engineered metal-mediated interactions between proteins can be reversibly broken by chelators of specific metal ions, ,− though connections to the cell state are less direct. In other studies, control of protein assembly by light and by ligand binding have been explored. , With DNA nanotechnology, a cage opened by ligand binding has been described .…”

Section: Introductionmentioning

confidence: 99%

Designing Protease-Triggered Protein Cages

Miller¹,

Srinivasan²,

Dharmaraj³

et al. 2022

J. Am. Chem. Soc.

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Proteins that self-assemble into enclosed polyhedral cages, both naturally and by design, are garnering attention for their prospective utility in the fields of medicine and biotechnology. Notably, their potential for encapsulation and surface display are attractive for experiments that require protection and targeted delivery of cargo. The ability to control their opening or disassembly would greatly advance the development of protein nanocages into widespread molecular tools. Toward the development of protein cages that disassemble in a systematic manner and in response to biologically relevant stimuli, here we demonstrate a modular protein cage system that is opened by highly sequence-specific proteases, based on sequence insertions at strategically chosen loop positions in the protein cage subunits. We probed the generality of the approach in the context of protein cages built using the two prevailing methods of construction: genetic fusion between oligomeric components and (non-covalent) computational interface design between oligomeric components. Our results suggest that the former type of cage may be more amenable than the latter for endowing proteolytically controlled disassembly. We show that a successfully designed cage system, based on oligomeric fusion, is modular with regard to its triggering protease. One version of the cage is targeted by an asparagine protease implicated in cancer and Alzheimer's disease, whereas the second version is responsive to the blood-clotting protease, thrombin. The approach demonstrated here should guide future efforts to develop therapeutic vectors to treat disease states where protease induction or misregulation occurs.

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“…Molecular self-assembly is one of the most distinct and costeffective way of producing structurally ordered and higher order architectures in nature. [1,2] Each building block interacts together through at least one or more molecular units to make self-assemblies. With the structural uniqueness and methodology, much effort has been made to create diverse selfassemblies with new functionality, such as DNA origami, protein assemblies, and organic/inorganic nanomaterials, [3][4][5] for use in wide-ranging fields including gene/drug delivery, vaccines, biosensors, diagnosis, and therapy of diseases.…”

Section: Introductionmentioning

confidence: 99%

Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery

Kim

Bae

Gijeong

et al. 2022

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Protein assemblies have drawn much attention as platforms for biomedical applications, including gene/drug delivery and vaccine, due to biocompatibility and functional diversity. Here, the construction and functionalization of a protein assembly composed of human clathrin heavy chain and light chain for a targeted protein delivery, is presented. The clathrin heavy and light chains are redesigned and associated with each other, and the resulting triskelion unit further self‐assembled into a clathrin assembly with the size of about 28 nm in diameter. The clathrin assembly is dual‐functionalized with a protein cargo and a targeting moiety using two different orthogonal protein–ligand pairs through one‐pot reaction. The functionalized clathrin assembly exhibits about a 900‐fold decreased KD value for a cell‐surface target due to avidity compared to a native targeting moiety. The utility of the clathrin assembly is demonstrated by an efficient delivery of a protein cargo into tumor cells in a target‐specific manner, resulting in a strong cytotoxic effect. The present approach can be used in the creation of protein assemblies with multimodality.

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Design of metal-mediated protein assemblies via hydroxamic acid functionalities

Cited by 17 publications

References 90 publications

De Novo Design of Polyhedral Protein Assemblies: Before and After the AI Revolution

De Novo Design of Polyhedral Protein Assemblies: Before and After the AI Revolution

Designing Protease-Triggered Protein Cages

Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery

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