
Design of a hyperstable 60-subunit protein icosahedron - te_platt
http://www.nature.com/nature/journal/v535/n7610/full/nature18010.html
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davi
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.

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.

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.

~~~
dekhn
I doubt you could avoid diffusion in these proteins to the point you desire.
It would be worth looking into species that exploit cryptobiosis, specifically
anhydrobiosis (rotifers, tardigrades, daphnia, and C. Elegans are all
examples). In most cases they can dessicate extremely, some of them by
exchanging glucose or water with trehalose (itself a fascinating topic worth
further study), so i wonder if you could make trehalose binding sites inside
the body.

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pierrec
Ouch, that comment: _Those are not icosahedra; they 're dodecahedra. A regular
icosahedron has 20 faces and 12 vertices._

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'll have to issue a
rather embarrassing errata stating the very title was wrong.

And an unrelated but equally bewildering thing: the page has this "editor's
pick" section containing a uselessly gigantic 5672x1823px image resized to
280x90px. What the fuck.

~~~
dekhn
I'm guessing here, but it's probably because dodecahedra have icosahedral
symmetry
([https://en.wikipedia.org/wiki/Icosahedral_symmetry](https://en.wikipedia.org/wiki/Icosahedral_symmetry))
and dodecahedrons are the dual of icosahedrons (see the row equating them
here:
[https://en.wikipedia.org/wiki/Capsid#Triangulation_number](https://en.wikipedia.org/wiki/Capsid#Triangulation_number))

Realistically it's most likely that Baker is using the terminology from
crystallography and virus studies, consistent with his background.

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derogator
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.

A topic like this suffers from high barriers that prevent the formation of
opinions, whereas today's Pardon Snowden thread[0] provides ample opportunity
for lengthy editorials.

[0]
[https://news.ycombinator.com/item?id=12494998](https://news.ycombinator.com/item?id=12494998)

------
lrc
Reminds me of the Andromeda Strain (except that didn't have any amino acids)

[http://mymeaningfulmovies.blogspot.com/2015/02/the-
andromeda...](http://mymeaningfulmovies.blogspot.com/2015/02/the-andromeda-
strain.html)

------
OrthoMetaPara
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't interfere
with the cage assembly process.

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).

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's just a simple idea).

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.

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imdsm
Could someone ELI-human? Ta

~~~
stephengillie
They made a really big, really stable molecule, inside an E Coli bacterium.

~~~
toufka
That is producible in huge quantities on demand (for the cost of sugar,
sunlight and water). That is defined with atomic specificity. And can have
appendages and payloads of arbitrary (genetic) sequence attached to it (again
with atomic specificity).

~~~
lohankin
"... attached to it with atomic specificity" \- and then what?

~~~
pazimzadeh
Enzymes and substrates could be grouped together so that they work more
efficiently (don't have to bump around looking for each other in a large
space).

Synthetic machinery that we design could be made functional inside the protein
complex so as not to disturb background cellular processes.

Receptors for specific cell types could be attached to the outside so that the
complex is taken up and a payload is delivered.

