A single residue can modulate nanocage assembly in salt dependent ferritin

Abstract

Modifications to a protein cage whose assembly depends on the presence of metal ions can modulate the extent of its dependence and in some cases convert the assembly to be salt independent.

Directed Compartmentalization of Mg2+ and Carbonic Anhydrase by Designed Three-Dimensional Protein Crystalline Frameworks for Efficient Conversion of CO2 into Nanoparticles

“…48,49 Consequently, the alkaline-earth cations are bound on the inner surface of the ferritin nanocage by interacting with acidic amino acid residues at the C 3 −C 4 interface. 33,50 Based on the above structural features, it appears that the Mg 2+ -mediated TmFtn shell-like architectures are an ideal platform for the synthesis of MgCO 3 nanoparticles because such natural spheroidal cages provide not only a rigidly confined space but also microenvironments with a high Mg 2+ concentration that favors carbonate mineral precipitation reactions once encountering carbanions, thereby realizing carbon biomineralization spontaneously. On the other hand, each ferritin molecule has eight hydrophilic threefold channels connecting the cavity and the protein exterior.…”

“…Fortunately, ubiquitous iron storage protein, ferritin, raises such possibility because it is usually composed of 24 similar subunits assembling into an approximate nearly spherical nanocage with an outer diameter of ∼12 nm and an inner cavity of ∼8 nm. Because of the existence of such a nanocage, ferritin has been explored for the fabrication of inorganic nanoparticles except for iron nanoparticles. − Different from typical ferritin, Thermotoga maritima ferritin (TmFtn) naturally occurs as a dimer showing an unusual alkaline-earth cation mediated assembly property, namely, the dimer tends to assemble into a normal 24-meric hollow protein nanocage in response to Ca 2+ or Mg 2+ . , Consequently, the alkaline-earth cations are bound on the inner surface of the ferritin nanocage by interacting with acidic amino acid residues at the C 3 – C 4 interface. , …”

Protein encapsulation within the internal cavity of a bacterioferritin

“…42,49 In the case of the Ftns from A. fulgidus and T. maritima , an Asp residue (Asp65) that is not generally conserved (and which is not conserved in E. coli Bfr) was found to play a key role in modulating the proteins’ assembly state response to salt concentration. 50,51 Therefore, whilst the conditions required to induce dissociation of Bfr are similar to those for the Ftns the physical basis for the change in association state appears to differ between the two classes of ferritin. Our data suggest that one consequence of this is a significantly reduced rate of inter-conversion between the oligomeric forms of Bfr.…”

Multifaceted Applications of Ferritin Nanocages in Delivering Metal Ions, Bioactive Compounds, and Enzymes: A Comprehensive Review

“…129,130 Diverging from conventional animal and plant ferritin nanocages, recent reports highlight the discovery of a novel class of bacterial ferritins in bacterium Thermotoga maritima, which intriguingly exhibits salt-dependent assembly characteristics. 25,131 More precisely, these bacterial ferritins disassociate into dimers at low ionic strengths and further reassemble into 24-mer nanocages at high salt concentrations. 132 This unique reversible assembly characteristic offers the potential for a simple and relatively mild strategy for enzyme encapsulation.…”

“…Ferritin is a ubiquitous protein found in various organisms, including vertebrates, plants, and microorganisms . Typically, ferritin is arranged in a symmetrical octahedral shape (2/3/4) to form a spherical shell with exterior and inner diameters of 12 and 8 nm, respectively. − This roughly spherical cage-like shape is made up of 24 subunits, each containing different helices (A, B, C, and D) and a short fifth E-helix. ,− The subunits combine to form six 4-fold and eight 3-fold channels with pore diameters ranging from 0.3 to 0.5 nm that connect the internal and exterior environments in a single ferritin molecule . Ferritin can be deprived of the inner iron atoms to form apoferritin, which is an empty ferritin cage without iron while sustaining its molecular dimension.…”