AARS Protein Fragment Segmentation for Novel Signaling Discovery
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Solution Overview
Problem
Aminoacyl-tRNA synthetases (AARS) have primarily been studied for their role in protein translation, with their full-length sequences well-characterized, but their protein fragments have not been systematically analyzed for novel biological activities, limiting their potential as biotherapeutic agents or diagnostic targets for various diseases.
Innovation Solution
Identification and characterization of protein fragments of AARS, referred to as 'resectins,' which exhibit non-canonical biological activities such as extracellular signaling, through methods like mass spectrometry, deep sequencing, and recombinant genetic engineering, enabling their use in diagnostic, drug discovery, and therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If full-length AARS sequences are studied for aminoacylation function, then biochemical characterization is improved, but discovery of novel biological activities is limited
Solution Approach 1:
The patent applies segmentation by dividing the full-length AARS protein into functional domains and fragments. Specifically, it identifies and characterizes separate functional regions including the aminoacylation domain and signaling domains, allowing independent study of each region's specific activities. This segmentation enables discovery of novel signaling activities that are masked in the full-length protein context.
Solution Approach 2:
The patent extracts and isolates specific protein fragments from the full-length AARS sequence that possess novel biological activities. By taking out specific domains (such as the signaling domain separate from the aminoacylation domain), the patent enables independent characterization and therapeutic development of fragments with non-canonical activities that were previously undetectable in the context of the full-length protein.
2Reliability
If AARS are considered essential housekeeping proteins, then their role in protein translation is confirmed, but their potential as drug targets is reduced
Solution Approach 1:
The patent segments the AARS protein into distinct functional domains, separating the essential aminoacylation function from novel signaling functions. This allows the signaling domains to be targeted independently as therapeutic agents while preserving the essential housekeeping function of the full-length protein, thereby maintaining both reliability and therapeutic potential.
Solution Approach 2:
The patent extracts and develops therapeutic agents based on specific protein fragments that mediate non-canonical signaling activities. These extracted fragments can serve as drug targets or therapeutic molecules without interfering with the essential aminoacylation function, thus resolving the contradiction between essentiality and therapeutic potential.
3Productivity
If systematic analysis of AARS fragments is not conducted, then research focus remains on canonical functions, but discovery of biotherapeutic agents is limited
Solution Approach 1:
The patent performs preliminary computational analysis and domain architecture studies of AARS proteins before initiating experimental work. By pre-identifying potential signaling domains and functional regions through sequence analysis and structural prediction, the patent can efficiently direct experimental resources to the most promising fragments for biotherapeutic development, thereby resolving the contradiction between research efficiency and therapeutic discovery.
Data Source
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AI summary
Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.