Fc-binding protein acid stability via amino acid substitution
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Solution Overview
Problem
Wild-type human FcγRIIa lacks sufficient acid stability, which is a limitation for industrial applications and storage.
Innovation Solution
Specific amino acid substitutions and deletions in the Fc-binding protein, such as Leu190Ser, improve acid stability, and the protein is produced using a method involving error-prone PCR and immobilized on an insoluble carrier for antibody adsorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type human FcγRIIa is used, then the protein maintains natural binding function, but acid stability is insufficient for industrial applications
Solution Approach 1:
The patent applies parameter changes by substituting specific amino acid residues (e.g., L190S, L63P, Q69L, P83L, I45T, T123P, N75S) in the FcγRIIa protein sequence to improve acid stability. These point mutations modify the protein's chemical properties without fundamentally changing its structure or function, enabling industrial application while maintaining natural binding function.
2Reliability
If multiple amino acid substitutions are introduced to improve acid stability, then acid resistance increases, but protein structure complexity increases
Solution Approach 1:
The patent applies local quality by introducing amino acid substitutions at specific, localized positions (e.g., positions 190, 63, 69, 83, 45, 123, 75) rather than throughout the entire protein sequence. This targeted approach improves acid stability while minimizing overall structural complexity and maintaining the protein's fundamental architecture.
Data Source
AI summary
An Fc-binding protein having at least amino acid residues of the extracellular domain of the amino acid sequence of wildtype human FcγRIIa (UniProt Accession Number: P12318) wherein the amino acid residues in the domain have an amino acid substitution or deletion at at least a specific position, a method for producing the protein, and an antibody adsorbent using the protein.