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Updated: Jul 13, 2026
11:39
Identification of Functional Protein Regions Through Chimeric Protein Construction
Published on: January 8, 2019
The design and characterization of two proteins with 88% sequence identity but different structure and function
Patrick A Alexander1, Yanan He, Yihong Chen
1Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA.
Summary
Researchers redesigned proteins with high sequence identity but distinct structures, revealing a simplified code for conformational switching and protein function. This finding suggests protein evolution may be more adaptable than previously thought.
Area of Science:
- Protein engineering
- Structural biology
- Biophysics
Background:
- Understanding protein folding and function is crucial for molecular biology.
- Natural proteins often exhibit complex structures and specific functions.
- Identifying the minimal sequence requirements for protein structure and function remains a challenge.
Purpose of the Study:
- To investigate a simplified code for conformational switching in proteins.
- To design homologous proteins with distinct tertiary structures and functions.
- To explore the relationship between protein sequence, structure, and function.
Main Methods:
- Redesign of natural proteins to achieve high sequence identity (88%) but different folds (3-alpha helix and alpha/beta).
- Characterization of protein structural properties using Nuclear Magnetic Resonance (NMR) spectroscopy.
- Assessment of conformational stabilities and ligand-binding affinities (IgG and serum albumin).
Main Results:
- Successfully designed two homologous heteromorphic proteins with distinct folds and retained native binding activities.
- Demonstrated that two different functions (IgG and albumin binding) can be encoded within a small subset of amino acids (7 of 56).
- Showcased that a limited number of amino acid interactions can dictate protein conformation and function, impacting protein structure prediction and evolution.
Conclusions:
- A simplified code for conformational switching exists, concentrated in a few key amino acids.
- Protein structure and function are highly sensitive to subtle sequence variations.
- The evolution of new protein folds and functions may occur more readily than previously assumed.
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