The retro-GCN4 leucine zipper sequence forms a stable three-dimensional structure

Area of Science:

• Protein structure and folding
• Biochemistry
• Structural biology

Background:

• The stability of proteins with inverted natural sequences is a key question in molecular biology.
• Leucine zippers are known to form stable helical coiled-coils.

Purpose of the Study:

• To investigate the structural consequences of inverting the natural sequence of the GCN4 leucine zipper.
• To determine if an inverted protein sequence can adopt a stable fold.

Main Methods:

• X-ray crystallography was used to determine the 3D structure.
• The crystal structure was resolved at a resolution of 2.1 angstroms.

Main Results:

• The retro-GCN4 leucine zipper formed a stable, parallel four-helix bundle.
• This structure is distinct from the two-stranded helical coiled-coil of the natural GCN4 leucine zipper.

Conclusions:

• An inverted protein sequence can adopt a stable and distinct fold.
• The determined structure of the retro-leucine zipper provides a basis for further structural and functional investigations.