Related Experiment Video
Updated: May 27, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
Published on: January 26, 2024
Intra-chain 3D segment swapping spawns the evolution of new multidomain protein architectures
András Szilágyi1, Yang Zhang, Péter Závodszky
1Institute of Enzymology, Hungarian Academy of Sciences, Karolina út 29, H-1113 Budapest, Hungary.
New protein architectures evolve through segment swapping between similar domains. This process, identified in 32 segment-swapped proteins (SSPs), offers insights into protein evolution and function.
Area of Science:
- Structural biology
- Protein evolution
- Bioinformatics
Background:
- Multidomain proteins evolve via domain concatenation.
- Structural domains can consist of multiple chain segments.
- Novel evolutionary mechanisms for protein architecture are actively researched.
Purpose of the Study:
- To investigate the evolution of multidomain proteins through 3D segment swapping.
- To identify and characterize segment-swapped proteins (SSPs) in the Protein Data Bank (PDB).
- To elucidate the evolutionary mechanisms and functional implications of segment swapping.
Main Methods:
- Comprehensive structural search of the PDB.
- Identification of 32 well-defined segment-swapped proteins (SSPs).
- Large-scale comparative analyses using structural alignment and hidden Markov model methods.
Main Results:
- Identified 32 SSPs across 18 structural families.
- Estimated that nearly 13% of multidomain proteins may have segment-swapped precursors.
- Found that domain swapping and fusion (DSF) is the predominant evolutionary mechanism, with circular permutation (CP) being less common.
- Segment swapping imparts directed flexibility and contributes to new protein functions.
Conclusions:
- Inter-domain segment swapping is a novel mechanism for generating new protein folds and multidomain architectures.
- SSPs possess unique structural and functional properties warranting their classification as a distinct group.
- Segment swapping plays a significant role in protein evolutionary innovation.
Related Concept Videos
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Conservation of Protein Domains
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Mechanisms of Membrane Domain Formation
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
Protein Folding
