“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 #PS32, 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
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
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*
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
This afternoon I'm learning about CRISPR/Cas9 at #ps32!
Biophysics of the p53 tumour suppressor. Accessible healthcare in post-industrial USA. Higher- and med-ed. MD/PhD candidate at SUNY Upstate, Syracuse NY.
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