Department of Systems Biology, Harvard Medical School, Boston, United States; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, United States; Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
Benjamin J Orlando
Department of Cell Biology, Harvard Medical School, Boston, United States
Department of Systems Biology, Harvard Medical School, Boston, United States; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, United States
Department of Cell Biology, Harvard Medical School, Boston, United States
Jules Gardener
Center for Nanoscale Systems, Harvard University, Cambridge, United States
David C Bell
Center for Nanoscale Systems, Harvard University, Cambridge, United States; School of Engineering and Applied Sciences, Harvard University, Cambridge, United States
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States
Maofu Liao
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, United States; Department of Cell Biology, Harvard Medical School, Boston, United States
Pamela A Silver
Department of Systems Biology, Harvard Medical School, Boston, United States
Iron storage proteins are essential for cellular iron homeostasis and redox balance. Ferritin proteins are the major storage units for bioavailable forms of iron. Some organisms lack ferritins, and it is not known how they store iron. Encapsulins, a class of protein-based organelles, have recently been implicated in microbial iron and redox metabolism. Here, we report the structural and mechanistic characterization of a 42 nm two-component encapsulin-based iron storage compartment from Quasibacillus thermotolerans. Using cryo-electron microscopy and x-ray crystallography, we reveal the assembly principles of a thermostable T = 4 shell topology and its catalytic ferroxidase cargo and show interactions underlying cargo-shell co-assembly. This compartment has an exceptionally large iron storage capacity storing over 23,000 iron atoms. Our results reveal a new approach for survival in diverse habitats with limited or fluctuating iron availability via an iron storage system able to store 10 to 20 times more iron than ferritin.
