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Buried polar residues in coiled-coil interfaces
D L Akey1, V N Malashkevich, P S Kim
1Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Biochemistry
|May 24, 2001
Summary
Researchers studied coiled coils, protein structures crucial for many functions. They found that introducing polar residues into the hydrophobic core can alter coiled coil geometry and stability.
Area of Science:
- Protein Structure and Dynamics
- Biochemistry
- Molecular Biology
Background:
- Coiled coils are prevalent protein structural motifs, comprising 3-5% of genomic residues.
- They feature a characteristic heptad repeat (abcdefg)n, with a and d positions forming the inter-helical interface.
- Approximately 20% of these interface residues are polar or charged, deviating from a purely hydrophobic nature.
Purpose of the Study:
- To investigate the impact of single polar residues at the coiled coil interface on protein stability and oligomeric specificity.
- To structurally characterize how these polar residues influence local packing and overall coiled coil geometry.
Main Methods:
- Construction of GCN4-p1 coiled coil variants with single polar residues (Asn, Gln, Ser, Thr) at a or d positions.
- Measurement of variant stability and oligomeric specificity.
- Determination of crystal structures for specific variants (e.g., with Thr or Ser).
Main Results:
- Single polar residues at interface positions significantly affect coiled coil stability and oligomeric specificity.
- Crystal structures reveal that polar residues alter local packing and influence global coiled coil geometry.
- Changes in Crick supercoil parameters and core cavity volumes were observed due to polar residue incorporation.
Conclusions:
- Polar residues within the hydrophobic core of coiled coils play a critical role in modulating their structural properties.
- Understanding these effects is vital for predicting and engineering protein structures and functions.
- This study provides structural insights into the tolerance and impact of non-canonical residues in protein interfaces.