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An evolutionary bridge to a new protein fold.
M H Cordes1, R E Burton, N P Walsh
1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature Structural Biology
|December 2, 2000
Summary
The Arc repressor N11L mutant acts as an evolutionary bridge, dynamically switching between beta-sheet and helical structures. This protein flexibility is influenced by environmental factors and ligand binding.
Area of Science:
- Protein structure and dynamics
- Molecular evolution
- Biophysics
Background:
- The Arc repressor protein exists in wild-type (beta-sheet) and 'switch Arc' (helical) conformations.
- The N11L mutation creates an intermediate state, Arc-N11L, bridging these two structures.
Purpose of the Study:
- To investigate the conformational flexibility of the Arc-N11L mutant.
- To understand the role of the N11L mutation in protein evolution.
- To elucidate the factors influencing the equilibrium between different Arc conformations.
Main Methods:
- Characterization of the Arc-N11L mutant protein.
- Analysis of structural transitions and dynamics.
- Investigation of environmental and ligand-binding effects on protein conformation.
Main Results:
- Arc-N11L can adopt both wild-type and mutant conformations.
- Structural exchange occurs on the millisecond timescale, indicating a dynamic equilibrium.
- The equilibrium is sensitive to temperature, solvent conditions, and ligand binding.
- Leucine (in N11L) integrates into the helical core or occupies a surface position, while Asparagine (in wild-type) is excluded from the helical core.
Conclusions:
- The N11L mutation facilitates evolutionary adaptation by enabling a transition from beta-sheet to helical structures.
- Arc-N11L serves as a crucial evolutionary intermediate, demonstrating plasticity in protein folding.
- Environmental and binding conditions modulate protein structure, highlighting the dynamic nature of protein function.