Related Experiment Video
Updated: Jun 30, 2026
09:51
Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
NMR structures of two designed proteins with high sequence identity but different fold and function
Yanan He1, Yihong Chen, Patrick Alexander
1Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA.
Summary
Researchers designed proteins with high sequence identity but different 3D structures, revealing key residues that dictate protein folding and the evolution of new protein folds.
Area of Science:
- Structural biology
- Protein folding
- Biochemistry
Background:
- Understanding protein sequence's role in 3D structure is crucial.
- Designing proteins with high sequence identity but different folds helps identify fold-specific codes.
Purpose of the Study:
- To determine the 3D structures of two designed proteins, G(A)88 and G(B)88, with 88% sequence identity but distinct folds.
- To elucidate the structural basis for fold switching and the role of nonidentical residues.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the 3D structures in solution.
- Comparative analysis of residue geometries in G(A)88 and G(B)88.
Main Results:
- Detailed 3D structures of G(A)88 (3-alpha fold) and G(B)88 (alpha/beta fold) were determined.
- Seven nonidentical residues were identified as critical for maintaining distinct fold topologies.
- Further mutations in these residues led to proteins with 95% sequence identity and different folds.
Conclusions:
- A small number of mutations can induce conformational switching to alternative, stable protein folds.
- This finding has significant implications for understanding the protein folding code and the evolution of protein structures.
Related Concept Videos
01:22Protein Folding
Overview
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
02:26Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
02:47Protein Families
Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism. Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members. If these new proteins contain similar amino acids in key locations, protein...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...