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Weekly Reading: Regulated N-glycosylation controls chaperone function and receptor trafficking (Ma etal.,Science386,667–672(2024))

The original article is here :  Regulated N-glycosylation controls chaperone function and receptor trafficking | Science

One of my past research projects involved oligosaccharyltransferase (OST). Personally, I do not like working with transmembrane enzymes, like OST, but  one thing that's always intrigued me about OST or other post-translational modification synthetic enzymes (e.g. O-GlcNAc transferase), is their promiscuity—how do these enzymes work on such a wide variety of substrates?

I mean, this paper is not about enzymology of OST, but the central question the paper ask in the introduction section is  compelling: Can the activity of OST be modulated by other factors? Researchers figured out the N-terminal region of HSP90B1 (ER chaperone) plays a regulatory role in modulating OST activity. Essentially, they propose that this region can act as a pseudo-substrate, inhibiting the glycosylation activity of OST. Very cool! 

How did evolution shape HSP90B1’s N-terminal region to have this regulatory function (I wish I knew about this, but nah, I stopped to think since I am in the thanksgiving weekend)?

On a more technical note, this paper presents a solid set of results without relying on flashy techniques. The abundance of Western blots might feel a bit overwhelming (I really don’t enjoy running them myself), but I have to admit—these blots are very pretty. 

I am a bit curious could more supporting data from—such as mass spectrometry-based cross-linking or co-immunoprecipitation (Co-IP)—be used to confirm the interactome between these proteins? Of course, I’ve never done these types of experiments myself, but I remember one of my previous labmates explaining the concept of cross-linking mass spectrometry, and I wonder if this could be an ideal follow-up experiment. That being said, given that some of these proteins, like the translocon, form transient complexes, a Co-IP might be tricky to pull off effectively.   

FYI This may be the good summary of paper!


(Which loop of STT3A is interacting with CCDC134? It may be  EL5 loop?)

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