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An extended hydrophobic core induces EF-hand swapping
M Håkansson1, A Svensson, J Fast
1Molecular Biophysics, Center for Chemistry and Chemical Engineering, Lund University, S-221 00 Lund, Sweden. Maria.Hakansson@mbfys.lu.se
Protein Science : a Publication of the Protein Society
|April 24, 2001
Summary
Mutated calbindin D(9k) forms stable, intertwined dimers through 3D domain swapping. This structural change, driven by hydrophobic interactions, is resistant to dilution but reversible by heating, revealing high energy barriers.
Area of Science:
- Structural Biology
- Protein Chemistry
- Biochemistry
Background:
- Calbindin D(9k) is a monomeric protein with two EF-hand calcium-binding domains.
- Protein misfolding and aggregation can lead to altered structures and stability.
- Domain swapping is a known mechanism of protein structural rearrangement.
Purpose of the Study:
- To determine the structure of a mutated calbindin D(9k) protein.
- To investigate the mechanism and stability of 3D domain-swapped calbindin D(9k) dimers.
- To understand the role of specific mutations in protein structural transitions.
Main Methods:
- X-ray crystallography at 1.8-Å resolution.
- Structural analysis of mutated calbindin D(9k).
- Investigation of dimer stability and conversion to monomers.
Main Results:
- Mutated calbindin D(9k) forms an intertwined 3D domain-swapped dimer.
- EF-hands are exchanged between monomers in the dimer structure.
- A hydrophobic cluster promotes monomer to dimer conversion.
- Dimers are stable and resistant to dilution but can be converted to monomers by heating.
Conclusions:
- Specific mutations induce 3D domain swapping in calbindin D(9k).
- Hydrophobic interactions play a key role in promoting domain swapping.
- The calbindin D(9k) dimer represents a stable, misfolded-like aggregate with high energy barriers for monomerization.