Localized unfolding at the junction of three ferritin subunits. A mechanism for iron release?

• Published in: The Journal of biological chemistry Vol. 273; no. 30; p. 18685
• Main Authors: Takagi, H, Shi, D, Ha, Y, Allewell, N M, Theil, E C
• Format: Journal Article
• Language: English
• Published: United States 24-07-1998
• Subjects: Amino Acid Substitution; Animals; Crystallography, X-Ray; Ferritins - genetics; Ferritins - metabolism; Iron - metabolism; Kinetics; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Folding; Ranidae; Spectrophotometry, Atomic; Structure-Activity Relationship
• ISSN: 0021-9258
• DOI: 10.1074/jbc.273.30.18685

How and where iron exits from ferritin for cellular use is unknown. Twenty-four protein subunits create a cavity in ferritin where iron is concentrated >10(11)-fold as a mineral. Proline substitution for conserved leucine 134 (L134P) allowed normal assembly but increased iron exit rates. X-ray crystallography of H-L134P ferritin revealed localized unfolding at the 3-fold axis, also iron entry sites, consistent with shared use sites for iron exit and entry. The junction of three ferritin subunits appears to be a dynamic aperture with a "shutter" that cytoplasmic factors might open or close to regulate iron release in vivo.