Structural characterization of encapsulated ferritin provides insight into iron storage in bacterial nanocompartments

Abstract

Ferritins are ubiquitous proteins that oxidise and store iron within a protein shell to protect cells from oxidative damage. We have characterized the structure and function of a new member of the ferritin superfamily that is sequestered within an encapsulin capsid. We show that this encapsulated ferritin (EncFtn) has two main alpha helices, which assemble in a metal dependent manner to form a ferroxidase center at a dimer interface. EncFtn adopts an open decameric structure that is topologically distinct from other ferritins. While EncFtn acts as a ferroxidase, it cannot mineralize iron. Conversely, the encapsulin shell associates with iron, but is not enzymatically active, and we demonstrate that EncFtn must be housed within the encapsulin for iron storage. This encapsulin nanocompartment is widely distributed in bacteria and archaea and represents a distinct class of iron storage system, where the oxidation and mineralization of iron are distributed between two proteins.DOI: http://dx.doi.org/10.7554/eLife.18972.001

Prokaryotic nanocompartments form synthetic organelles in a eukaryote

“…In vivo protein encapsulation is guided by short targeting peptides (TPs), which are located at the C-termini of cargo proteins. A large variety of native cargo proteins has been identified in bacteria and archaea, including peroxidases and ferritin-like proteins involved in stress response pathways 11,[14][15][16] . Using Escherichia coli as a host, it has been shown that packaging of non-native proteins into the encapsulins from Thermotoga maritima and Brevibacterium linens can be achieved by fusion of targeting peptides to the intended cargo 17,18 .…”

Conservation of the structural and functional architecture of encapsulated ferritins in bacteria and archaea

“…The encapsulated ferritins ( EncFtn ) are recently described members of the ferritin superfamily (1–3). These proteins are sequestered within encapsulin nanocompartments, and the two proteins act in concert to provide an iron storage system with a much greater capacity than the classical ferritins and DNA-binding Protein from Starved cells (DPS) nanocages (3, 4).…”

Structure and function of a 9.6 megadalton bacterial iron storage compartment

“…A newly discovered class of protein organelles called encapsulin nanocompartments are implicated in microbial iron and redox metabolism and have so far only been shown to be involved in oxidative stress response (10)(11)(12)(13). Previously reported encapsulins share an HK97 phage-like fold and self-assemble from a single capsid protein into icosahedral compartments between 24 and 32 nm in diameter with triangulation numbers of T = 1 (60 subunits) and T = 3 (180 subunits), respectively (11,12,14).…”