ERAD in 3 different ways

Well I was going to write about J. Weissman's new paper, but Pedro (from our lab) published his work TODAY (I knew it was coming out soon ...)

His paper and YET ANOTHER paper from the Weissman group made the cover of the latest issue of Cell:

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They deal with the nitty-gritty of ERAD (to learn more on ERAD see this morning's post).

I won't go through the Weissman paper (the one in Cell that is), as I've yet to read it, but I can give you the summary of Pedro's work.

He discovered that ERAD works through three different complexes. Each complex is responsible for pulling a different class of misfolded protein out of the ER. Here is a diagram from a review by David Eng:

i-5f4693287652dbebc35b97d466d9333d-ERAD.jpg

The first complex, comprised of Doa1+other proteins, pulls out membrane bound proteins whose cytosolic domain (cytosolic = outside the ER) is misfolded. This has now been called ERAD-C.

The second complex is made up of a bunch of proteins, with Hrd1/Hrd3 comprising the core of the complex (see the diagram from David Eng's review) and is responsible for pulling out proteins whose membrane bound domain is misfolded. This is ERAD-M.

Finally the last complex (similar to the second complex + a couple of extra factors, such as Der1/Yos9/Usa1) retrieves proteins whose luminal domain (lumen = inside the ER) is misfolded ... and yes this is now called ERAD-L.

So there you have it. Three machines, for three different tasks.

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