Alan boosted

“For this part, we’re just going to crouch in the corner of the deck. This forces the program to render Moriarty into the wardrobe which we locked in chapter 3. From there we can easily carry the wardrobe (ignore his screaming) all the way to Reichenbach Falls and toss him over. This triggers the alternate ending which is 38 seconds shorter”

Starts with rapid (~10^2ms) reversible engagement of ubiquitinated substrate, followed by slower (~1ms) insertion of the target protein C-terminus that triggers rapid proteasome cap rearrangement to engage deubiquitinase. Sequential deubiquitinase proceed rapidly compared to first. Proteolysis of the naked chain is limited by rate of unfolding, otherwise turns over very quickly.

Excellent talk from Prof Martin (Berkeley) to start day three of , deconvoluting how the 26S proteasome actually works through some kinetic analysis that warms this chemist's heart.

And within each of those, a very cool two-step domain duplication mechanism explains patterns of divergence

Making a strong case that despite those similarities, these proteins represent convergence from several evolutionary origins.

This talk is doing a great job grounding points in the familiar and quickly building out to the unfamiliar

Dr. Slusky (Kansas) is puzzling out how bacterial outer membrane proteins, no matter the function, almost all seem to look the same: right handed contiguous beta barrels.

Now we're right up my alley: adjacent repeat domains generally have lower sequence identity than the average, to avoid fragment-exchange complementation misfolding... Except for SHIRT domains

Strep Gordonni SHIRT-domain repeat proteins form similarly rigid structures to project colonization domains away from the bacterial surface.

Staph Aureus SasG protein assumes extremely high aspect-ratio rigid rods that project from the bacterial outer membrane, which mediate clustering and biofilm-formation

Switching tracks to hear about repetitive bacterial surface proteins from Prof Potts (York, UK), who tackles the other tool of supervisor: biofilms

Prof Jiang (Berkeley) buried the lede of his (excellent) structural talk: timed treatment with anti-CRISPR agents can enhance nucleolytic specificity.

I thought CRISPR was special for targeted cutting-and-pasting. Dr Joung is telling us about literal directed mutagenesis (deamination) of bases themselves. Mind *blown*

Once again, I can't tell which parts of this talk are new and exciting, and which parts are just new to me.

"My institution says I have financial conflicts that must be declared." Buddy, there are six different biotechs listed on that slide. You shouldn't need to be told that requires disclosure.

Woah: none of the anti-CRISPR proteins are transported with the virus. The viral genes have to race to be transcribed before the bacterium chews them up

Perhaps unsurprisingly, viral proteins wedge themselves in to every part of CRISPR function. They're particularly good at mimicking deformed DNA in acquisition and nuclease sites

Prof Wiedenheft opening the session with a structural journey across all the ways viruses inhibit the CRISPR/Cas9 system. (Reminder: for the billion years prior to becoming a gene-editing tool, CRISPR/Cas9 were part of bacterial immune systems)

This afternoon I'm learning about CRISPR/Cas9 at !

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