Iron Biomineral Growth from the Initial Nucleation Seed in L‐Ferritin

X‐ray structures of homopolymeric human L‐ferritin and horse spleen ferritin were solved by freezing protein crystals at different time intervals after exposure to a ferric salt and revealed the growth of an octa‐nuclear iron cluster on the inner surface of the protein cage with a key role played by some glutamate residues. An atomic resolution view of how the cluster formation develops starting from a (μ3‐oxo)tris[(μ2‐glutamato‐κO:κO’)](glutamato‐κO)(diaquo)triiron(III) seed is provided. The results support the idea that iron biomineralization in ferritin is a process initiating at the level of the protein surface, capable of contributing coordination bonds and electrostatic guidance. Initial step of ferritin‐assisted iron biomineralization: L‐type subunits in mammalian ferritins are known to facilitate iron mineralization by providing nucleation sites but the atomic‐level mechanism of the mineral formation remains elusive. Time‐resolved X‐ray crystallography was successfully used to observe iron cluster growth starting from an initial (μ3‐oxo) triiron seed anchored to glutamate residues on the inner ferritin cage.