Ying Dong

PI at Guangzhou lab | Structural immunology | Former postdoc at Harvard Medical School, Boston Children's Hospital @WuLabHarvard

[Prof. Hao Wu @WuLabHarvard]

Excited to share an amazing video on the NLRP3 inflammasome pathway generated by talented Ann from the Iwasa lab @janetiwasa @Ann_HuiLiu. It shows the real cryo-EM structures of the pathway from #NLRP3, #ASC, #caspase-1, #GSDMD, #IL-1b, to #NINJ1. #cryoem @LeXiao17 Enjoy

[Ying Dong @yingdong01]

@ShiyuXia @UCBerkeley @UCB_Chemistry Congrats Shiyu! I'm so happy for you :)

[Kay Lab @LEK_Lab]

Take a look at our most recent collaboration with @WuLabHarvard & @jkagan1 Labs! Jeff did some very cool NMR structural work of pro-IL-18 & contrasted it with Cryo-EM data and assays done by @yingdong01 & @pascal_devant. Enjoy!

[Ying Dong @yingdong01]

@LironDavid2 @ImmunityCP @jkagan1 @LEK_Lab @WuLabHarvard Thank you, Liron!

[Ying Dong @yingdong01]

Ever wondered how different caspases select their substrates? Turns out, they have their own styles. Check out our study: https://t.co/a27xIZX6oC @ImmunityCP Cheers to the fantastic teamwork! @jkagan1 @LEK_Lab @WuLabHarvard. 🥳🧵(1/7)

[Ying Dong @yingdong01]

@manikrpc @WuLabHarvard @ImmunityCP @jkagan1 @LEK_Lab Thank you, Manik!

[Ying Dong @yingdong01]

@YuHuibin @ImmunityCP @jkagan1 @LEK_Lab @WuLabHarvard Thank you!

[Ying Dong @yingdong01]

@pascal_devant @WuLabHarvard @LEK_Lab @ImmunityCP I lile the way you call it a yoga!

[Ying Dong @yingdong01]

@jkagan1 @LEK_Lab @WuLabHarvard @pascal_devant Thank you Jon. Congrats to us all!

[Jonathan Kagan @jkagan1]

Caspase-1 has a special way to interact with IL-18. So pleased to work with my long collaborator Hao Wu and new collaborator Lewis Kay on this project.
Tweetorial by the fabulous Ying Dong:
https://t.co/nWtm2He5Ej

[Ying Dong @yingdong01]

7/7 1. Last but not least, even a much-advanced version of AlphaFold - 3 fails to predict the structure of pro-IL18 alone and pro-IL18 in the complex. We let our data speak for itself.

[Ying Dong @yingdong01]

5/7 By performing structural analysis, we conclude that the binding interface of IL-18 by its IL-18R receptor will only be built till caspase-1 cleavage. This elucidates the essential role of caspase cleavage in enabling the mature form of IL-1 to achieve its biological activity.

[Ying Dong @yingdong01]

6/7 You may be surprised to see how huge the conformational change before and after cleavage:

[Ying Dong @yingdong01]

4/7 What pro-IL-18 would be like before catching by caspase-1? We solved the pro-IL-18 apo structure by solution NMR. Courtesy to my amazing collaborator @ Jeff Bonin. Surprisingly, it is a compact structure just like it is in the complex.

[Ying Dong @yingdong01]

3/7 We investigated at the cellular level and in vitro — courtesy to my amazing collaborator @pascal_devant. Surprisingly, we found that caspase-1 depends on exosite less than active site to perform cleavage on pro-IL-18 ( this differs from caspase-4).

[Ying Dong @yingdong01]

2/7 We revealed two major forms of binding, where two binding interfaces (active site and exosite) are involved differently. To figure out the roles of these two interfaces, we performed mutagenesis studies.

[Ying Dong @yingdong01]

1/7 caspase-1 is known to recognize a wider range of substrates than caspase-4. We found that caspase-1 forms a stable complex with pro-IL-18, like caspase-4. Interestingly, we observed various modes of binding between caspase-1 and pro-IL-18.

[Prof. Hao Wu @WuLabHarvard]

I am excited to share with you the Wu Lab Reunion video by Kara @jf033! 27 featured structures and the 27-year journey! Seeing trainees from all over the world doing the best science is the ultimate reward as a mentor! I am proud!

[Liron David @LironDavid2]

Thrilled to share our exciting paper on #NINJ1 published in @CellCellPress. NINJ1 acts as "🍪cutter" by cutting and releasing membrane disks leading to lytic cell death. https://t.co/bUbgKeBX0g
Congrats to the amazing team-@WuLabHarvard
@BobbyHollings @JazlynBorges @LabSteinberg

[Ying Dong @yingdong01]

@LironDavid2 @CellCellPress @WuLabHarvard @BobbyHollings @JazlynBorges @LabSteinberg Liron, congrats to you and the team! You are amazing! I'm so happy for you! 🥳🥳🥳