Grant's Anatomy

by Christoph
 

Figure 1. M. magnetotacticum magneto­somes arranged by cytoskeletal filament MamK; still at 00:31 of movie. Fronti­s­piece: still at 00:20 of movie. Source

At an EMBO workshop in Copen­ha­gen in 2006 on 'Cell cycle and cy­to­ske­le­tal ele­ments in bac­te­ria,' I was al­most un­able to stay put in my seat dur­ing one pre­sen­ta­tion: Grant Jen­sen showed the 3D-mon­tage of cryoET ima­ges of mag­ne­to­somes in Mag­ne­to­spi­ril­lum mag­ne­to­tac­ti­cum. It was a vi­su­al jour­ney in­to and through the in­ter­ior of a cell, and en­ti­re­ly bas­ed on the re­sults de­scrib­ed in their pa­per (Fi­gure 1, and Fron­ti­spie­ce). Ad­mit­ted­ly, I was ne­ver par­ti­cu­lar­ly im­pres­sed by the mo­vie Fan­tas­tic Vo­yage, but these here weren't stunts, trick shots or CGI ani­ma­tions, un­avail­able in 1966. These were re­al da­ta! Pro­ces­sed with com­pu­ta­tion­al­ly in­ten­sive al­go­rithms, not­with­stand­ing. Per­haps you can re­late to my en­thu­si­asm af­ter you view the 34‑se­cond vi­deo, it is still avai­l­able on You­tube.
 

That was in 2006, and Grant Jen­sen was keen to point out that bet­ter re­so­lu­tion and con­trast were not yet pos­sible, and, al­most as an ex­cuse, stat­ed that elec­tron-dense mag­ne­to­somes were a par­ti­cu­lar­ly easy stu­dy ob­ject. To­day, cryo­gen­ic elec­tron mi­cro­sco­py (cryo-EM) is a bur­geon­ing field in­volv­ing many labs (not gob­bling up as much re­search mon­ey as the Large Had­ron Col­li­der (LHC) but still...) Cryo-EM and, more spe­ci­fi­cal­ly, elec­tron cryo­to­mo­gra­phy (cryoET) with sub­to­mo­graph­ic av­er­ag­ing achieve re­so­lu­tions in the range of a few Ång­ström (1 Å=0.1 nm) that were pre­vious­ly re­serv­ed for pro­tein crys­tal­lo­graph­ers. And crys­tal­lo­graph­ers and mi­cro­scop­ists "meet" suc­cess­ful­ly in this re­alm of near-atom­ic re­so­lu­tion: Xiang et al. (2021), for ex­ample, vir­tu­al­ly "carv­ed-out sten­cils" from crys­tal da­ta in the PDB col­lect­ion to un­mis­tak­ab­ly pin­point ri­bo­som­es in­clud­ing their ori­en­ta­tion in elec­tron cryo­to­mo­grams of E. coli cells (see here in STC.)
 

Figure 2. Cryo-ET tomo­gram of a B. burg­­dor­fe­ri cell. Che­mo­re­cep­tor ar­ray (blue), fla­gel­lar mo­tor (yel­low), Out­er mem­­brane ve­sicle-chain (pink). Scale Bar 100 nm. (Click ima­ge for the un-an­no­tat­ed ori­gi­nal.) Cour­te­sy of Ari­a­ne Brie­gel

As a technique, cryoET was − and still is − in­stru­ment­al in elu­ci­dat­ing the fine struc­ture of mem­brane‑bound ma­cro­mo­le­cul­ar pro­tein com­plex­es like fla­gel­lar mo­tors or the F pil­us-as­so­ciat­ed plat­forms for con­ju­ga­tion (see here in STC.) As you may know, crys­tal­lo­graph­ers re­gu­lar­ly tore their hair out when it came to mem­brane-bound pro­tein com­plex­es. But CryoET could do even more, vi­sua­liz­ing struc­tures that other imag­ing tech­ni­ques could not and thus did not find. I am talk­ing about the 'che­mo­sen­so­ry ar­rays' that were dis­cover­ed and tho­rough­ly stu­died by Aria­ne Brie­gel and co-work­ers in the Jen­sen lab (and now in her lab at Lei­den Uni­ver­si­ty, NL.) Brief­ly, these ar­rays re­pre­sent the so­phis­ti­cat­ed ar­ran­ge­ment of cel­lu­lar re­cept­ors for ex­tra­cel­lu­lar sign­als that are, via a phos­pho­re­lay, trans­mit­ted to the fla­gel­lar mo­tor to trig­ger, or un-trig­ger, fla­gel­lar ro­ta­tion. Struc­ture meets funct­ion, you might say. Fi­gure 2 shows a che­mo­sen­so­ry ar­ray of B. burg­dor­fe­ri in side view, you can see the top-view of E. co­li and Tre­po­ne­ma ar­rays here. (An aside. Cer­tain­ly not in 2006, but now I tend to see a mem­brane-at­tach­ed che­mo­sen­so­ry ar­ray api­cal to the cell tip on the right at 00:04 sec in the M. mag­ne­to­tac­ti­cum video.)
 

Figure 3. Cell division in Caulobacter cres­centus, FtsZ ring formation. Screenshot from Source

Now the Jensen lab have sum­ma­riz­ed and struc­tur­ed their work − and that of their nu­mer­ous col­la­bor­a­tors − of the last fif­teen-or-so years in a mile­stone pub­li­ca­tion, The At­las of Bac­te­ri­al & Ar­chae­al Cell Struc­ture. As the au­thors say: "The book ad­dres­ses a fun­da­ment­al gap in ex­ist­ing text­books, name­ly, what bac­te­ri­al and ar­chae­al cells look like" at near-atom­ic re­so­lu­tion, "and how the ma­cro­mo­le­cul­ar struc­tur­es they con­tain give rise to their di­verse and comp­lex funct­ions." It does not take much to pre­dict that this a­tlas will be to mi­cro­bio­lo­gists what Gray's Ana­to­my is to phy­si­cians, and a wel­come up­grade of The Cell by D.W. Faw­cett (2nd. Ed.,1981), the stand­ard work for the elec­tron mi­cro­sco­py of cells, main­ly eu­kar­yot­ic cells.
 

The atlas is expli­cit­ly meant as stu­dy ma­ter­ial for stu­dents and teach­ers as "the in­ter­ac­tive, mul­ti­me­dia re­sour­ce feat­ures real da­ta from more than 150 cells be­long­ing to ap­pro­xi­ma­te­ly 70 dif­fer­ent spe­cies, imag­ed by cut­ting-edge cryo­gen­ic elec­tron mi­cros­co­py (cryo-EM). Com­ple­men­ta­ry ani­ma­tions show the cel­lu­lar ma­chine­ry in act­ion." I en­courage STC read­ers to dive in­to the at­las right away by click­ing cell­struc­ture­at­las.org. This is pos­sible with­out prior re­gis­tra­tion and at no cost, as the Jen­sen lab has pub­lish­ed the at­las, host­ed by the Cal­tech Li­bra­ry, un­der the Crea­tive Com­mons CC BY-NC 4.0 li­cense.