Structural and dynamic characterization of the hexa-coordinated globin from Spisula solidissima

Area of Science:

• Biochemistry
• Structural Biology
• Neuroscience

Background:

• Nervous systems have high energy demands, necessitating continuous oxygen supply.
• Globin proteins, specifically nerve hemoglobins (nHbs), facilitate oxygen transport in invertebrate nerve cells.
• nHbs are found at high concentrations and possess oxygen affinities similar to vertebrate myoglobins.

Purpose of the Study:

• To elucidate the structural basis of nerve hemoglobin function in invertebrates.
• To determine the crystal structure of the nerve hemoglobin from Spisula solidissima (SsHb).
• To investigate the structural dynamics and ligand-binding properties of SsHb.

Main Methods:

• X-ray crystallography was used to determine the three-dimensional structure of SsHb.
• Molecular Dynamics (MD) simulations were performed on monomeric and dimeric SsHb.
• Simulations covered various heme coordination states: bis-histidyl hexa-coordinated, deoxy penta-coordinated, and O2-bound hexa-coordinated.

Main Results:

• The crystal structure of SsHb reveals a dimeric form stabilized by a 4-helix bundle.
• SsHb exhibits a classic globin fold with bis-histidyl hexa-coordination of the heme-iron atom.
• MD simulations showed distinct structural rearrangements at the dimer interface, influencing conformational fluctuations and internal cavities.

Conclusions:

• The structural findings suggest a distal site opening mechanism facilitating ligand access to the heme.
• The dimer interface's structural and dynamic properties are hypothesized to play a role in SsHb's ligand binding cooperativity.
• This research provides critical insights into the structure-function relationship of invertebrate nerve hemoglobins.