Discover and read the best of Twitter Threads about #CDlab
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Protein sequencing is a big deal and goes way beyond DNA sequencing. While we have ~20000 protein-coding genes, we have _millions_ of protein variants, mainly because of post-translational modifications that attach a side group to amino acids.
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Phosphorylation is the most frequent PTM, and of particular interest, as dysregulation of phosphorylation pathways is linked to many diseases including cancers, Parkinson’s, Alzheimer’s, and heart disease.
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We lack techniques to measure such PTMs on the single-molecule level! 😳
=> We need new single-molecule techniques
(Mass spectrometry requires typically more than a billion copies and often struggles to identify the correct position of a PTM between multiple candidate sites)
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=> We need new single-molecule techniques
(Mass spectrometry requires typically more than a billion copies and often struggles to identify the correct position of a PTM between multiple candidate sites)
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Today, we put 2 new #CDlab papers on the @arxiv preprint server – which both report, in different ways, on demonstrating nanoscale rotary motors that are driven by a flow through a nanopore.
arxiv.org/pdf/2206.06612…
arxiv.org/pdf/2206.06613…
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arxiv.org/pdf/2206.06612…
arxiv.org/pdf/2206.06613…
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@arxiv Such rotors are inspired by the awesome F0F1 ATPase motor protein in our cells. Here, a proton gradient drives rotation of F0 which induces conformational changes in F1 that catalyze production of ATP, which is the fuel for most processes in our body.
Video credit Biovisions
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Video credit Biovisions
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We built similar rotary motors synthetically from the bottom up, using ‘DNA origami’ in great collaboration with @hendrik_dietz lab. These motor structures dock onto a nanopore and autonomously show sustained unidirectional rotations where a rod rotates at >10 rotations/sec.
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Today we publish a paper in @ScienceMagazine that expands nanopore readings to the proteome:
a nanopore-based scanner to read off PROTEINS at the single-molecule level! 🤩
Awesome experiments by postdoc Henry Brinkerhoff of our #CDlab, with MD simulations of @aksimentievLab
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a nanopore-based scanner to read off PROTEINS at the single-molecule level! 🤩
Awesome experiments by postdoc Henry Brinkerhoff of our #CDlab, with MD simulations of @aksimentievLab
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@ScienceMagazine @aksimentievLab Here’s the link to this paper in @ScienceMagazine entitled “Multiple re-reads of single proteins at single-amino-acid resolution using nanopores”: science.org/doi/10.1126/sc…
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@ScienceMagazine @aksimentievLab Principle reminds of nanopore DNA sequencing: we draw a peptide through a nanopore with a helicase walking on a lead DNA strand, and then read off ion current step signals as amino acids are blocking the pore.
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