Structure of human ferritin L chain

Area of Science:

• Biochemistry
• Structural Biology
• Biophysics

Background:

• Ferritin is the primary intracellular iron-storage protein, crucial for iron homeostasis.
• It comprises 24 subunits (heavy H and light L chains) forming a spherical shell.
• H-rich ferritins oxidize iron(II), while L-rich ferritins manage iron(III) nucleation and storage.

Purpose of the Study:

• To elucidate the structure of recombinant human L-chain ferritin (HuLF).
• To investigate the iron nucleation and transport pathways within the ferritin capsid.
• To provide structural insights for neutron diffraction studies using perdeuterated HuLF.

Main Methods:

• X-ray crystallography was used to determine two crystal forms of HuLF.
• Native and perdeuterated proteins were utilized for structural analysis.
• Structural data was analyzed to identify key residues and pathways.

Main Results:

• The structures reveal acidic residues at the ferrihydrite nucleation site and iron channel.
• An ordered cadmium (Cd2+) structure was observed within the iron transport channel.
• A previously disordered loop (between helices D and E) is clearly visible in the HuLF structures.

Conclusions:

• The findings offer detailed insights into the mechanism of iron transport into the ferritin core.
• The identified structural features provide a basis for understanding L-chain ferritin's role in iron storage.
• Perdeuterated HuLF crystals are prepared for future neutron diffraction studies, enabling further structural characterization.