Related Experiment Video
Updated: Aug 16, 2025
08:59
Analysis of Protein Folding, Transport, and Degradation in Living Cells by Radioactive Pulse Chase
Published on: February 12, 2019
11.3K
Creative destruction: New protein folds from old
Claudia Alvarez-Carreño1,2, Rohan J Gupta2, Anton S Petrov1,2
1NASA Center for the Origin of Life, Georgia Institute of Technology, Atlanta, GA 30332-0400.
Summary
Protein folds evolve through "creative destruction," where gene fusion creates new protein structures from ancestral domains. This mechanism explains the diversity of protein folds and has implications for understanding genetic instability in diseases like cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Evolutionary Biology
Background:
- Protein fold evolution is a central question in biological sciences.
- While incremental mutation explains similar folds, diverse folds suggest other mechanisms.
- Sequence and structure similarities hint at common ancestry between distinct protein folds.
Purpose of the Study:
- To investigate the evolutionary relationships between distinct protein folds.
- To propose a novel mechanism for protein fold evolution and divergence.
- To explore the implications of this mechanism for disease states.
Main Methods:
- Comparative analysis of sequence and structure similarity between protein folds.
- Identification of common ancestry between distinct β-barrel folds: SH3, OB, and CLB.
- Development of a theoretical model for fold evolution termed 'creative destruction'.
Main Results:
- Evidence of common ancestry was found between the SH3, OB, and CLB β-barrel folds.
- A mechanism termed 'creative destruction' was proposed, involving gene fusion and domain merging.
- This mechanism explains fold interconversion, circular permutation, and partial inheritance of ancestral motifs.
Conclusions:
- Creative destruction offers a model for the emergence and divergence of diverse protein folds.
- The model explains how fused polypeptides explore new folding landscapes while retaining ancestral features.
- This mechanism is relevant to understanding fused proteins in cancer and genetic instability.
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