A change-in-hand mechanism for S100 signalling

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• S100 proteins are a large subclass of EF-hand calcium-binding proteins.
• They are proposed to function as intracellular calcium modulatory proteins, similar to troponin-C and calmodulin.

Purpose of the Study:

• To elucidate the three-dimensional structures of S100A6 and S100B in apo- and calcium-bound states.
• To identify and characterize novel calcium-induced conformational changes in S100 proteins.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to determine protein structures.
• Analysis of apo- and calcium-bound forms of S100A6 and S100B.

Main Results:

• The study identified a novel calcium-induced conformational change, termed the "change-in-hand" mechanism.
• This mechanism involves the reorientation of Helix III in the C-terminal calcium-binding loop.
• In S100B, this reorientation exposes a hydrophobic patch, suggesting a protein-protein recognition site.

Conclusions:

• The "change-in-hand" mechanism is a key feature of S100 protein function.
• The identified interaction site on S100B provides a structural basis for its role in protein-protein recognition.
• Structural insights into S100 proteins advance understanding of calcium signaling pathways.