Structural characterization of human S100A16, a low-affinity calcium binder

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• S100 proteins are a family of calcium-binding proteins involved in various cellular processes.
• Human S100A16 is a less-studied member of the S100 protein family.
• Understanding the structural basis of S100A16's function, particularly its calcium-binding properties, is crucial.

Purpose of the Study:

• To determine the three-dimensional structure of human S100A16 in its apo and calcium(II)-bound states.
• To investigate the conformational changes of S100A16 upon calcium binding.
• To elucidate the molecular determinants underlying S100A16's calcium-binding affinity and structural stability.

Main Methods:

• X-ray crystallography for solid-state structure determination.
• Nuclear Magnetic Resonance (NMR) spectroscopy for solution-state structure determination.
• Structural comparison and analysis of apo and calcium(II)-bound forms.

Main Results:

• The homodimeric structure of human S100A16 was determined in both solid and solution states, showing good agreement.
• The solution structure of calcium(II)-bound S100A16 revealed only minor conformational rearrangements compared to apo S100A16.
• S100A16 exhibits weak calcium(II) binding affinity, attributed to the absence of a key glutamate residue in the N-domain binding site.
• Stronger hydrophobic interactions within S100A16 stabilize its closed conformation, resisting disruption by calcium binding.

Conclusions:

• Human S100A16 possesses a unique structural stability that limits conformational changes upon calcium binding.
• The absence of a glutamate ligand and enhanced hydrophobic interactions contribute to S100A16's distinct calcium-binding properties.
• These findings differentiate S100A16 from other S100 proteins and provide a structural basis for its functional characteristics.