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Yousuf A. Khan

@yousufakhan.bsky.social

1.4K followers 250 following 51 posts

Group Leader @Stanford. RNA focused ML/AI, cryoEM/ET, and biophysics. Formerly:DeepMind AlphaFold,EvoscaleAI, Churchill Scholar@Cambridge_Uni & seen on Netflix

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Yousuf A. Khan @yousufakhan.bsky.social · Aug 27

I'm extremely thrilled to announce that I will be starting as a group leader at Stanford this upcoming fall! My lab will be studying how RNAs exert themselves in the cell to induce a multitude of biological phenomena using ML, cryoEM/ET, and biochemistry!

www.yousufakhan.com

Yousuf A. Khan (YAK) Lab - RNA Research at Stanford University

Yousuf A. Khan (YAK) Lab - Studying RNA folding, interactions, and cellular effects using Molecular and Cellular Physiology, Structural Biology, and Machine Learning at Stanford University

www.yousufakhan.com

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Yousuf A. Khan @yousufakhan.bsky.social · 1d

This paper was a tour de force and would not be possible without he help of so many collaborators like @juanbonifacino.bsky.social and many more. Thank you!!!

Yousuf A. Khan @yousufakhan.bsky.social · 1d

Strikingly, the presence of this frameshifted proteoform was necessary for myocardial contraction, as we showed in PLEKHM2-KO cells that required both the WT and frameshifted proteoforms to recover fully, leading to our model

Yousuf A. Khan @yousufakhan.bsky.social · 1d

Furthermore, we were able to show that this frameshifted version of PLEKHM2 generated a hyper-active version of this protein, which did not require activation of its canonical activator

Yousuf A. Khan @yousufakhan.bsky.social · 1d

Not only did the frameshift exist, it was highly conserved and encoded for an additional alpha-helix domain

Yousuf A. Khan @yousufakhan.bsky.social · 1d

Today our journey ends! We were able to find a highly conserved cellular +1 PRF signal in the gene PLEKHM2/SKIP

Yousuf A. Khan @yousufakhan.bsky.social · 1d

A few years ago, we published in Nature (nature.com/articles/s41...) detailing this artefact and noting that no true PRF signal existed in humans gave access to two overlapping open reading frames that both encoded something useful like in viruses

Yousuf A. Khan @yousufakhan.bsky.social · 1d

However the authors (nature.com/articles/nat...) and others in the field had unfortunately been using a reporter with a malicious splicing artefact, accidentally presenting PRF activity.

Yousuf A. Khan @yousufakhan.bsky.social · 1d

PRF is employed widely across viral clades from HIV-1, Sars-COV-2, RSV, Influenza, etc. However, there was always a chase to find the first real case of PRF occurring in a human, cellular gene. And in 2014, researchers believed that had found the first case in CCR5

Yousuf A. Khan @yousufakhan.bsky.social · 1d

Programmed Ribosomal Frameshifting (PRF) is a phenomena that has been studied extensively in viruses since the 80s. In short, a single RNA has the ability to code for multiple proteins by 'recoding' the genetic code i.e. having the ribosome change its reading frame mid-elongation

Yousuf A. Khan @yousufakhan.bsky.social · 1d

Excited to announce the YAK lab's first paper and the discovery of the FIRST human cellular PRF signal to give access to two overlapping open reading frames (science.org/doi/10.1126/...)! Before we dive in, the story actually begins in a Nature from 11 years ago

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Yousuf A. Khan @yousufakhan.bsky.social · 13d

Excited to announce that I have been selected to receive a High-Risk, High-Reward grant from the NIH to help support the research our lab does at the intersection of AI and molecular biology to study RNA. Read more about here: news.stanford.edu/stories/2025...

Stanford researchers receive NIH High-Risk, High-Reward grants

This year’s awardees are researching cancer treatments, age-related disease, and much more.

news.stanford.edu

Yousuf A. Khan @yousufakhan.bsky.social · Aug 27

Excited to collaborate and have people join us! Please checkout the lab website above if you are interested!

Yousuf A. Khan @yousufakhan.bsky.social · Aug 27

Yousuf A. Khan (YAK) Lab - RNA Research at Stanford University

Yousuf A. Khan (YAK) Lab - Studying RNA folding, interactions, and cellular effects using Molecular and Cellular Physiology, Structural Biology, and Machine Learning at Stanford University

www.yousufakhan.com

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Reposted by Yousuf A. Khan

Ahmad Jomaa @jomaalab.bsky.social · Aug 1

Check out our new preprint on the discovery of a molecular switch in NAC that mediates nascent chain sorting on the ribosome and prevents mitochondrial protein mistargeting by SRP. A great collaboration with the Shan Lab @Caltech and the Qi Lab @UVA: www.biorxiv.org/content/10.1...

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Yousuf A. Khan @yousufakhan.bsky.social · Jul 29

Don’t leave us hanging Hiten!

Reposted by Yousuf A. Khan

Alex Rubinsteyn @alexr.bsky.social · Jul 23

Going deep on 2A peptides:

www.cell.com/cell-reports...

(Trying to pick between GSG:T2A, GSG:P2A, and furin site:GSG:T2A)

Systematic identification and characterization of eukaryotic and viral 2A peptide-bond-skipping sequences

Rao et al. identified thousands of previously unknown 2A peptides across both viruses and eukaryotes using an HMMER analysis. The authors further identified a unique class of 2A peptides, class B, who...

www.cell.com

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Reposted by Yousuf A. Khan

Sergey Ovchinnikov @sokrypton.org · Jul 22

PSA = Google Colab Pro free for one year for academic use (US only):
blog.google/outreach-ini...

New Google Colab features for higher education

Google Colab offers free Colab Pro for students, interactive slideshows and AI controls in notebooks.

blog.google

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Reposted by Yousuf A. Khan

Nikolai Slavov @slavov-n.bsky.social · Jul 9

Key numbers in cell biology

Having a sense of scale helps to think more rigorously and realistically about biological systems.

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Reposted by Yousuf A. Khan

Nature Structural & Molecular Biology @natsmb.nature.com · Jul 3

ICYMI: New online: SNARE disassembly requires Sec18/NSF side loading

SNARE disassembly requires Sec18/NSF side loading

Nature Structural & Molecular Biology, Published online: 02 July 2025; doi:10.1038/s41594-025-01590-wKhan et al. show that Sec18 uses both D1 and D2 AAA+ rings cooperatively, opening them laterally for SNARE substrate loading and for subsequent release of SNAREs.

go.nature.com

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Reposted by Yousuf A. Khan

Hiten Madhani @hitenmadhani.bsky.social · Jul 2

Cool paper on bacterial amyloids as protection from predatory bacteria from the Whitely lab at CU Boulder.

There are predatory fungi, so one wonders if a similar system exists in eukaryotes.

www.nature.com/articles/s41...

Functional amyloid proteins confer defence against predatory bacteria - Nature

Escherichia coli uses curli fibres, oligomers of the functional amyloid CsgA, as a barrier to protect against the predatory bacteria Bdellovibrio bacteriovorus and Myxococcus xanthus in a mechanism th...

www.nature.com

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Yousuf A. Khan @yousufakhan.bsky.social · Jul 2

Thus, any kind of SNARE can be processed universally by this single molecule machine. Check out the paper for more in-depth structural work! (5/5)

Yousuf A. Khan @yousufakhan.bsky.social · Jul 2

Combining in-vivo mass-spec, single molecule FRET, and time resolved cryoEM, we were able to determine that this NSF/Sec18 ring actually splits itself open from the side to accomodate SNAREs, thus completely bypassing any substrate topology issues! (4/5)

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Yousuf A. Khan @yousufakhan.bsky.social · Jul 2

The complex that recycles these SNAREs is called NSF/Sec18. However, our mehanistic understanding of how these complex SNARE proteins are pulled through the NSF/Sec18 complex is poor. SNAREs are like a knotted thread that must somehow be threaded by a NSF/Sec18 needle (3/5)

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Yousuf A. Khan @yousufakhan.bsky.social · Jul 2

SNARE proteins are the engines for membrane fusion; they cause neurotransmitters to be released in a synpatic cleft all the way to the relase of hormones. After these SNAREs perform their job, they must naturally be recyled and prepared for additional rounds of fusion (2/5)

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Yousuf A. Khan @yousufakhan.bsky.social · Jul 2

Sharing some of my PhD work that just came out today.

TLDR; We found a universal mechanism for all the many kinds of SNAREs are processed and recycled by a single molecular machine that is conserved in all eukaryotic life as we know it (1/5)

www.nature.com/articles/s41...

(1/5)

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