Localized unfolding at the junction of three ferritin subunits. A mechanism for iron release?
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.
Department of Biochemistry, North Carolina State University, Raleigh, North Carolina 27695-7622, USA.
H
H
Takagi
D
D
Shi
Y
Y
Ha
N M
NM
Allewell
E C
EC
Theil
D019943:Amino Acid Substitution; D000818:Animals; D018360:Crystallography, X-Ray; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D011898:Ranidae; D013054:Spectrophotometry, Atomic; D013329:Structure-Activity Relationship
D005293:Ferritins; D007501:Iron