Inserted Peptide Regulation of Protein Function via Coiled-Coil Dimers
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Solution Overview
Problem
Existing methods for regulating protein function are limited in applicability and require extensive remodeling of target proteins, making them difficult to translate across diverse proteins for therapeutic and biotechnological applications.
Innovation Solution
Insertion of a non-structured peptide into a solvent-exposed loop of a target protein, followed by formation of a coiled-coil dimer with a regulatory peptide to disrupt protein function, and activation or inhibition through a regulatory peptide or proteolytic cleavage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing methods for regulating protein function are used, then protein activity can be controlled, but the methods are limited in applicability and require extensive remodeling of target proteins
Solution Approach 1:
The regulation system is segmented into separate functional components: a modular peptide insert sequence that can be independently introduced into target proteins, and distinct regulatory peptides that bind to the insert to achieve activation or inhibition. This segmentation allows the same insert mechanism to be applied across diverse proteins without requiring extensive remodeling of each target protein's structure.
Solution Approach 2:
The peptide insert sequence serves multiple functions: it acts as a binding site for regulatory peptides, serves as an allosteric regulation trigger, and can be introduced into diverse proteins at specific locations. The regulatory peptides themselves can activate or inhibit different target proteins through the same insert mechanism, providing universal applicability across various protein families and functions.
2Reliability
If existing regulation methods are applied, then protein function can be modulated, but they require extensive tuning for each target protein separately
Solution Approach 1:
The peptide insert is designed with specific local properties (hydrophobic residues at positions 3-7 and 13-18, charged residues at positions 1-2 and 19-22) that enable reliable binding of regulatory peptides. This localized structural design ensures consistent regulation effectiveness across different target proteins without requiring extensive tuning of the insert sequence itself.
Solution Approach 2:
The invention achieves regulation by changing the binding affinity parameter of the peptide insert through regulatory peptide binding, rather than changing the insert sequence itself. The regulatory peptides modulate the insert's conformational state and binding properties, providing reliable function modulation with minimal sequence changes required.
3Reliability
If a regulatory peptide binds to the inserted peptide forming a coiled-coil dimer, then the functional site of the target protein is disrupted by an allosteric effect, but the inserted peptide must be positioned precisely
Solution Approach 1:
The peptide insert sequence is pre-designed with specific structural features (hydrophobic core at positions 3-18, charged flanking regions) that enable it to automatically adopt the correct conformation and positioning when introduced into the target protein. The insert is positioned in solvent-exposed loops away from the functional site, and its binding to regulatory peptides is pre-configured to trigger the desired allosteric effect.
Solution Approach 2:
The peptide insert acts as an intermediary element between the regulatory peptide and the target protein's functional site. When the regulatory peptide binds to the insert, the insert transmits this binding event as an allosteric signal to the functional site, disrupting it indirectly. This intermediary mechanism provides reliable regulation without requiring direct positioning of the regulatory peptide at the functional site.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Provides a versatile method to regulate protein function, applicable to diverse proteins, enabling activation or inhibition with high specificity and efficiency, useful for pharmacological, therapeutic, diagnostic, and biotechnological applications.
Implementation Method 1
a coiled-coil dimer is formed between the regulatory peptide and an inserted peptide, changing its conformation from a random structure to the helical structure
Implementation Method 2
This locally disrupts the structure of the target protein and inhibits its function
Data Source
AI summary
The invention refers to the regulation of function of proteins through insertion of a peptide into the selected protein and its interaction with a regulatory peptide that interacts with the inserted peptide. The invention can be used to activate or inactivate the function of different selected proteins and therefore to regulate their properties and processes, useful for pharmacological, therapeutic, diagnostic, sensing, biotechnological and other industrial applications.