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Design of a hyperstable 60-subunit protein icosahedron

42 pointsby te_plattover 8 years ago

6 comments

daviover 8 years ago
Hey cool, 3rd author Shane Gonin is now at Janelia (where my lab is) and I know a bit about this work. Funny to see it pop up here.<p>The kind of electron microscopy (EM) of brain tissue I do relies upon embedding the tissue in a resin called Epon. Epon has excellent cutting properties and low intrinsic contrast in EM. But in order to embed tissue in Epon it has to be completely dehydrated, which quenches genetically expressed fluorphores like GFP.<p>My fantasy for these genetically expressed buckyball-like proteins is that one could engineer their interior to be sufficiently hydrophilic that GFP fluorescence would survive complete dehydration of the surrounding tissue, instead relying on the polarized residues of the amino acids in the interior. This would let us combine highest quality EM with highest quality light microscopy in the same sample -- which would be very useful indeed.
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pierrecover 8 years ago
Ouch, that comment: <i>Those are not icosahedra; they&#x27;re dodecahedra. A regular icosahedron has 20 faces and 12 vertices.</i><p>No matter how I look at it, it seems to be right. I wonder if they have a good reason for abusing nomenclature like that. Or perhaps they&#x27;ll have to issue a rather embarrassing errata stating the very title was wrong.<p>And an unrelated but equally bewildering thing: the page has this &quot;editor&#x27;s pick&quot; section containing a uselessly gigantic 5672x1823px image resized to 280x90px. What the fuck.
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derogatorover 8 years ago
For anyone paying attention, the dearth of comments in this thread is a key indicator that the most commented threads on HN are all bike shedding threads.<p>A topic like this suffers from high barriers that prevent the formation of opinions, whereas today&#x27;s Pardon Snowden thread[0] provides ample opportunity for lengthy editorials.<p>[0] <a href="https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=12494998" rel="nofollow">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=12494998</a>
lrcover 8 years ago
Reminds me of the Andromeda Strain (except that didn&#x27;t have any amino acids)<p><a href="http:&#x2F;&#x2F;mymeaningfulmovies.blogspot.com&#x2F;2015&#x2F;02&#x2F;the-andromeda-strain.html" rel="nofollow">http:&#x2F;&#x2F;mymeaningfulmovies.blogspot.com&#x2F;2015&#x2F;02&#x2F;the-andromeda...</a>
OrthoMetaParaover 8 years ago
The fact that you can tack on an extra protein domain to each protein subunit is really neat because it lets you assemble little macromolecules containing several custom functionalities. Presumably these extra domains face outwards, coating the surface of the cage. Hopefully these extra domains don&#x27;t interfere with the cage assembly process.<p>For example, say you created fusions between the cage mononmer and antibody Fv chains that bind two different proteins (A and B) and then you created fusions between the cage monomer and two different fluorescent proteins (GFP and RFP).<p>In bacteria strain 1, you express fusion A and fusion GFP so that you assemble cages that will show a green signal where-ever A is found (e.g., for fluorescent microscopy). Likewise, in bacterial strain 2, you expression fusions B and RFP so that you get a red signal where ever B is. You could use these as detectors in a western blot, for example. (Obviously there are better, established ways to detect proteins of interest in a western blot, but that&#x27;s just a simple idea).<p>Another idea that I remember reading about was creating glucuronidase fusions to antibody fragments designed to bind cancer cells. The patient would then be administered the glucuronide of a cytotoxic drug, which is not toxic in its glucuronide form. The idea is that the antibody fusion protein would activate the drug so that it would be concentrated highly near the cancer cell and nowhere else.
imdsmover 8 years ago
Could someone ELI-human? Ta
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