Self-assembly of globular proteins with intrinsically disordered protein polyelectrolytes and block copolymers

Horn, Justin M.; Zhu, Yuncan; Ahn, So Yeon; Obermeyer, Allie C.

doi:10.1039/d2sm00415a

Cited by 4 publications

(4 citation statements)

References 52 publications

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“…The disordering leads to high structural flexibility enabling IDPs and IDRs to be involved in biological functions and processes like the conversion of fibrinogen to fibrin, ribosomal assembly, or allosteric regulation. 3 Further, due to their biodegradability, their high tunability, and their ability to form various nanostructures, IDPs are of great interest as synthetic polymer substitutes, 4 scaffolds for tissue regeneration 5 or nanodrugs. 6 On the other hand, intrinsically disordered structures can assemble into well-defined structures, which can be beneficial for an organism, i.e., the gain of function such as in pili of bacteria.…”

Section: ■ Introductionmentioning

confidence: 99%

β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

et al. 2023

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Intrinsically disordered proteins (IDPs) play an important role in molecular biology and medicine because their induced folding can lead to so-called conformational diseases, where β-amyloids play an important role. Still, the molecular folding process into the different substructures, such as parallel/ antiparallel or extended β-sheet/crossed β-sheet is not fully understood. The recombinant spider silk protein eADF4(Cx) consisting of repeating modules C, which are composed of a crystalline (pep-c) and an amorphous peptide sequence (pep-a), can be used as a model system for IDP since it can assemble into similar structures. In this work, blend films of the pep-c and pep-a sequences were investigated to modulate the β-sheet formation by varying the molar fraction of pep-c and pep-a. Dichroic Fouriertransform infrared spectroscopy (FTIR), circular dichroism, spectroscopic ellipsometry, atomic force microscopy, and IR nanospectroscopy were used to examine the secondary structure, the formation of parallel and antiparallel β-sheets, their orientation, and the microscopic roughness and phase formation within peptide blend films upon methanol post-treatment. New insights into the formation of filament-like structures in these silk blend films were obtained. Filament-like structures could be locally assigned to βsheet-rich structures. Further, the antiparallel or parallel character and the orientation of the formed β-sheets could be clearly determined. Finally, the ideal ratio of pep-a and pep-c sequences found in the fibroin 4 of the major ampullate silk of spiders could also be rationalized by comparing the blend and spider silk protein systems.

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Section: ■ Introductionmentioning

confidence: 99%

β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

et al. 2023

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“…The hydrophilic ELP block enhances the solubility of the hydrophobic ELP block, thereby producing a temperature window in which protease-driven phase separation proceeds during an isothermal reaction. The hydrophilic block sequence design space is vast: hydrophilic ELP blocks containing polar or charged guest residues can increase the solubility of hydrophobic ELPs, as can hydrophilic tags or protein domains beyond ELPs. ,− As a technology, protease-driven ELP phase separation will benefit from systematic understanding of the role of the hydrophilic block sequence on the temperature window for protease-driven ELP phase separation. We further report four cleavable ELP variants responsive to tobacco etch virus protease, thrombin, factor Xa, and enterokinase, each of which undergoes isothermal phase separation upon incubation with the intended protease.…”

Section: Discussionmentioning

confidence: 99%

Protease-Driven Phase Separation of Elastin-Like Polypeptides

Wirtz,

Yun,

Wick

et al. 2024

Biomacromolecules

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Elastin-like polypeptides (ELPs) are a promising material platform for engineering stimuli-responsive biomaterials, as ELPs undergo phase separation above a tunable transition temperature. ELPs with phase behavior that is isothermally regulated by biological stimuli remain attractive for applications in biological systems. Herein, we report protease-driven phase separation of ELPs. Protease-responsive "cleavable" ELPs comprise a hydrophobic ELP block connected to a hydrophilic ELP block by a protease cleavage site linker. The hydrophilic ELP block acts as a solubility tag for the hydrophobic ELP block, creating a temperature window in which the cleavable ELP reactant is soluble and the proteolytically generated hydrophobic ELP block is insoluble. Within this temperature window, isothermal, protease-driven phase separation occurs when a critical concentration of hydrophobic cleavage product accumulates. Furthermore, protease-driven phase separation is generalizable to four compatible protease-cleavable ELP pairings. This work presents exciting opportunities to regulate ELP phase behavior in biological systems using proteases.

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“…This is because the information that a molecule localizes in both the nucleus and cytoplasm suggests a function of the transportation between them and post-transcriptional modification [3]. Recent progress in our understanding of the complex formation and intrinsically disordered (ID) proteins is changing views about the 3D conformation of protein complexes [4][5][6]. The flexibility and promiscuity of ID proteins in binding multiple partners have led to the realization that ID proteins can be hub proteins.…”

Section: Of 11mentioning

confidence: 99%

Splicing Modulators Are Involved in Human Polyglutamine Diversification via Protein Complexes Shuttling between Nucleus and Cytoplasm

Shimada

2023

IJMS

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Length polymorphisms of polyglutamine (polyQs) in triplet-repeat-disease-causing genes have diversified during primate evolution despite them conferring a risk of human-specific diseases. To explain the evolutionary process of this diversification, there is a need to focus on mechanisms by which rapid evolutionary changes can occur, such as alternative splicing. Proteins that can bind polyQs are known to act as splicing factors and may provide clues about the rapid evolutionary process. PolyQs are also characterized by the formation of intrinsically disordered (ID) regions, so I hypothesized that polyQs are involved in the transportation of various molecules between the nucleus and cytoplasm to regulate mechanisms characteristic of humans such as neural development. To determine target molecules for empirical research to understand the evolutionary change, I explored protein–protein interactions (PPIs) involving the relevant proteins. This study identified pathways related to polyQ binding as hub proteins scattered across various regulatory systems, including regulation via PQBP1, VCP, or CREBBP. Nine ID hub proteins with both nuclear and cytoplasmic localization were found. Functional annotations suggested that ID proteins containing polyQs are involved in regulating transcription and ubiquitination by flexibly changing PPI formation. These findings explain the relationships among splicing complex, polyQ length variations, and modifications in neural development.

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Self-assembly of globular proteins with intrinsically disordered protein polyelectrolytes and block copolymers

Abstract: Intrinsically disordered polypeptides are a versatile class of materials, combining the biocompatibility of peptides with the disordered structure and diverse phase behaviors of synthetic polymers. Synthetic polyelectrolytes are capable of...

Cited by 4 publications

References 52 publications

β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

Protease-Driven Phase Separation of Elastin-Like Polypeptides

Splicing Modulators Are Involved in Human Polyglutamine Diversification via Protein Complexes Shuttling between Nucleus and Cytoplasm

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