Sven Lange
@sven-m-lange.bsky.social
Structural Biochemist. Postdoc in Brown lab @ Harvard Med🇺🇸 with interest in ubiquitin. Formerly MRC PPU🇬🇧🏴 MPI Dortmund🇩🇪 Ruhr-Uni Bochum🇩🇪. He/Him.
That makes sense - do you still include the Ub during structure alignment though? As I guess that it should be excluded here and only used for rmsd benchmarking in the next step. For the branched triUb example on github it appears that alignment converged on an attached Ub instead of proximal Ub.
October 17, 2025 at 2:37 PM
That makes sense - do you still include the Ub during structure alignment though? As I guess that it should be excluded here and only used for rmsd benchmarking in the next step. For the branched triUb example on github it appears that alignment converged on an attached Ub instead of proximal Ub.
Very nice work! The RMSD of polyubiquitin chains may be biased by strong local alignment on one ubiquitin though, as I can see this happened for the Github example of the branched K11/K48-triUb. In the "no linker" (blue) case the proximal Ub is flipped and K48-Ub landed on K11-Ub and vice versa.
October 16, 2025 at 8:19 PM
Very nice work! The RMSD of polyubiquitin chains may be biased by strong local alignment on one ubiquitin though, as I can see this happened for the Github example of the branched K11/K48-triUb. In the "no linker" (blue) case the proximal Ub is flipped and K48-Ub landed on K11-Ub and vice versa.
This work was supported by a postdoctoral fellowship from the Sara Elizabeth O'Brien Trust, the Smith Family foundation, and funding from NIGMS. Last but not least, I would like to thank Alan for his mentorship and support over the last 2 years! @alanbrownhms.bsky.social 8/8
April 29, 2025 at 3:05 PM
This work was supported by a postdoctoral fellowship from the Sara Elizabeth O'Brien Trust, the Smith Family foundation, and funding from NIGMS. Last but not least, I would like to thank Alan for his mentorship and support over the last 2 years! @alanbrownhms.bsky.social 8/8
Our multidisciplinary approach, from proteomics to live-cell imaging, shows that CFAP36 is highly conserved across diverse ciliated organisms, pointing to a fundamental role in ciliary biology. 🌍 7/n
April 29, 2025 at 3:05 PM
Our multidisciplinary approach, from proteomics to live-cell imaging, shows that CFAP36 is highly conserved across diverse ciliated organisms, pointing to a fundamental role in ciliary biology. 🌍 7/n
CFAP36 uses "coincidence detection" to bind two IFT subunits only accessible in retrograde trains – ensuring one-way traffic out of cilia! We validated these interactions in vivo by introducing disruptive mutations in the predicted binding interfaces of CFAP36 and IFT - which stalled CFAP36. 6/n
April 29, 2025 at 3:05 PM
CFAP36 uses "coincidence detection" to bind two IFT subunits only accessible in retrograde trains – ensuring one-way traffic out of cilia! We validated these interactions in vivo by introducing disruptive mutations in the predicted binding interfaces of CFAP36 and IFT - which stalled CFAP36. 6/n
How does CFAP36 bind to retrograde IFT trains though? In an unbiased #AlphaFold2-multimer screen using pairwise predictions of ciliary proteins with CFAP36, we identified subunits of both the IFT-A and -B subcomplexes as potential binding partners. 5/n
April 29, 2025 at 3:05 PM
How does CFAP36 bind to retrograde IFT trains though? In an unbiased #AlphaFold2-multimer screen using pairwise predictions of ciliary proteins with CFAP36, we identified subunits of both the IFT-A and -B subcomplexes as potential binding partners. 5/n
Live cell #TIRF imaging of flagella revealed that CFAP36 prefers to travel with retrograde IFT trains moving back to the ciliary base. 4/n
April 29, 2025 at 3:05 PM
Live cell #TIRF imaging of flagella revealed that CFAP36 prefers to travel with retrograde IFT trains moving back to the ciliary base. 4/n
When CFAP36 is depleted in cells, we observed K63-linked ubiquitin accumulating in cilia and disruption of #Hedgehog signaling – a pathway vital for development. This highlights why precise protein export matters for proper signaling. 3/n
April 29, 2025 at 3:05 PM
When CFAP36 is depleted in cells, we observed K63-linked ubiquitin accumulating in cilia and disruption of #Hedgehog signaling – a pathway vital for development. This highlights why precise protein export matters for proper signaling. 3/n
We identified #CFAP36 as a missing link in ciliary protein homeostasis: it connects ubiquitinated proteins to the intraflagellar transport #IFT machinery for removal. But CFAP36 doesn’t act alone: it forms a complex with ARL3, a small GTPase previously known for its role during ciliary import. 2/n
April 29, 2025 at 3:05 PM