Be­yond the Bac­te­r­ial Micro­com­part­ment

by Merry Youle

Bac­te­r­ial mi­cro­com­part­ments were a great in­no­va­tion. As Alan Der­man ex­plained,  these pro­tein-bounded struc­tures as­sist with di­verse meta­bolic processes by hous­ing the req­ui­site en­zymes along with their sub­strates, se­ques­ter­ing po­ten­tially toxic in­ter­me­di­ates, and al­low­ing the prod­ucts to exit. But the story does not end there. En­ter the nanocom­part­ment.
 

A spec­trum of com­part­ments and en­zyme com­plexes. (A) Model of the ethanolamine uti­liza­tion (Eut) micro­compartment. (B) Model of the car­boxysome micro­compartment. © Shell struc­ture of T. mar­itima en­capsulin. (D) Shell struc­ture of B. sub­tilis lumazine syn­thase. (E) 3D re­con­struc­tion of bovine pyru­vate de­hy­dro­ge­nase com­plex. (F) Struc­ture of hu­man fer­ri­tin. Source

These are the sim­plest vari­a­tion known so far on the theme of bac­te­r­ial com­part­ments. Like the mi­cro ver­sion, these nano struc­tures are thin, icosa­he­dral pro­tein shells that en­close a spe­cific pro­tein pay­load. Here the shells are only 20–24 nm in di­am­e­ter, com­pared to the ~120 nm di­am­e­ter of the mi­cro­com­part­ments, and the shells are built from only 60 copies of a sin­gle pro­tein, en­cap­sulin. Turns out that the en­cap­sulins are a large and widely-dis­trib­uted fam­ily of pro­teins found in both the Bac­te­ria and the Ar­chaea. The first ones had been no­ticed a decade ago in cul­ture su­per­natants of My­cobac­terium tu­ber­cu­lo­sis and Bre­vibac­terium linens. How­ever, their struc­tural role in the build­ing of pro­tein shells was not dis­cov­ered un­til 2008 when Sut­ter and col­leagues in­ves­ti­gated the struc­ture of the cap­sulin of Ther­mo­toga mar­itima, a hy­per­ther­mophile from a very deep branch in the bac­te­r­ial lin­eage. (For a help­ful com­men­tary on the Sut­ter pa­per, click here.)

Struc­ture of the T. mar­itima nanocom­part­ment com­posed of 12 en­cap­sulin pen­tamers. (a) View from the out­side on the five-fold sym­me­try axis. One pen­tamer is high­lighted in cyan, with one monomer in red. (b) View to the in­side of the shell, which is cut open in the mid­dle and shown in a sur­face rep­re­sen­ta­tion. Source

The en­cap­sulins in the shell form 12 pen­tamers, each with a cen­tral pore a few angstroms in di­am­e­ter; other pores ex­ist be­tween ad­ja­cent pen­tamers, al­to­gether of­fer­ing sev­eral pos­si­bil­i­ties for se­lec­tive in­flux and exit. What could be the func­tion of such tiny com­part­ments? To get some clues, the re­searchers looked at the neigh­bor­hood around the en­cap­sulin genes in 49 bac­te­r­ial genomes. No vi­ral genes were ev­i­dent. In­stead, al­most all of the en­cap­sulin genes are con­ve­niently lo­cated in two-gene oper­ons along with a gene for an en­zyme in­volved in ox­ida­tive-stress re­sponse: ei­ther a heme-con­tain­ing dye-de­col­oriz­ing per­ox­i­dase or a fer­ritin-like pro­tein. (Fer­ritin-like pro­teins in bac­te­ria ox­i­dize toxic fer­rous iron to an in­sol­u­ble fer­ric form that is de­posited within the cav­ity formed by their mul­ti­meric struc­tures.) Sev­eral lines of ev­i­dence in­di­cate that those en­zymes are tar­geted to the nanocom­part­ments and re­side there (along with iron de­posits, in the case of the fer­ritin-like pro­tein).

For us vi­rophiles, a most in­trigu­ing prop­erty of the en­cap­sulin from T. mar­itima is its "re­mark­able" sim­i­lar­ity to some vi­ral cap­sid pro­teins — sim­i­lar­ity in both its ter­tiary struc­ture and its pro­tein-pro­tein in­ter­ac­tions. So that raises even more ques­tions: Who orig­i­nated these pro­teins, the viruses or the bac­te­ria, and when? No an­swers yet, leav­ing us free to spec­u­late and place charges of nano-theft.

Ref­er­ence

Sut­ter M, Boehringer D, Gut­mann S, Gün­ther S, Prangishvili D, Loess­ner MJ, Stet­ter KO, We­ber-Ban E, Ban N. (2008). Struc­tural ba­sis of en­zyme en­cap­su­la­tion into a bac­te­r­ial nanocom­part­ment. Na­ture struc­tural & mol­e­c­u­lar bi­ol­ogy, 15 (9), 939−947. PMID 19172747