So I’m trying to be punctual with this next science update. Today’s article comes from the journal, Nature. It discusses the structure of F-actin, or filamentous actin. Actin is a protein that polymerizes to form a long chain. In its non-polymerized state, it is known as G-actin, and in its polymerized state, is known as F-actin. Actin is very important for cell motility, muscle behavior, and a host of other functions. Many, many scientists now study actin, its dynamics, and proteins that interact with actin. For a simple review of actin, I recommend Wikipedia.
Anyway, let's get down to the heart of this paper: Direct visualization of secondary structures of F-actin by electron cryomicroscopy by Takashi Fujii and colleagues. Because this article was published in Nature, it is short. This provides a unique challenge for authors, as oftentimes scientists have much more to say about their work than they can squeeze into the limited confines of a Nature article. It is interesting to see what the authors view as the most important aspects of their work and what is relegated to the Supplemental Information.
The authors submit in this paper a methodology for using cryoelectron microscopy to get a high resolution structure of F-actin. They end up with a 6.6 Angstrom resolution, not nearly good enough to show side-chain conformations, but good enough to see the secondary structure and to arrange the individual actin subunits. In doing so, the researchers show that the individual F-actin subunits do undergo significant changes in structure compared to their structure as G-actin. And these comprise the two biggest findings of the group. The technical advancement and the structural advancement.
It's going to be difficult for me to discuss/critique the science to great lengths here, as the innovation and process the researchers took to get their results relied on advancing cryoelectron microscopy. That said, it seems like this technique could be applied to other thin biopolymers (On a side note: are there any others? Feel free to chime in and help me out, science friends!). The results here are more interesting to me anyway (than the technical aspect of how they got the results, though that's important). I thought they authors did a good job in this regard, leaving much of the technical aspect in the Supplementary Info and spending more of their time writing about the structure and its implications in actin behavior. The researchers also did a decent job at keeping the paper from sounding like your average structure-for-the-sake-of-structure paper. Their emphasis on the consequences of structural changes was welcome, and only for a couple of paragraphs did they revert to some of the basic interactions. All in all, the science was explained well and the importance/novelty of the work was appropriately emphasized.
Quick note on the figures. They were very good. Colorful and attractive, though also informative. The authors highlighted the most important structures and changes, and designed the figures appropriately.
The authors suggested the next logical step being to do cryoEM on F-actin with other proteins bound (those that interact with F-actin). While this is obviously something we as scientists would like to know (gives us new molecular interactions to target with drugs), I'm not sure how effectively one can coat these fibers. As the technique relies upon the repetitiveness of the polymer for its accuracy, getting efficient and regular binding along the fiber may be difficult, limiting the resolution of such a structure.
If I was to follow up on this article, I would run some simulations to determine how the thermodynamic stability of the actin monomer changes as it is incorporated into the filament, using this new structural model for F-actin. As the authors alluded to, it seems like the actin subunits of F-actin may be "spring-loaded" as they are incorporated. In other words, they adopt a less stable conformation that is supported by external contacts (interaction with other units of the polymer). Again, as the authors mentioned, this internal instability may help to explain actin dynamics in the cell.
Well, it's been a long weekend, so I'll wrap this up. This paper comes across as well written and informative. I'm not sure if the findings are quite Nature worthy, but are definitely worth giving a cursory glance. See you all next time!
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