Comments on: Peptide splicing, proteasomes, and immunity

By: Mystery Rays from Outer Space - Meddling with things mankind is not meant to understand. Also, pictures of my kids » Rube Goldberg and hypersensitivity: Frame-shifting, part II

Wed, 31 Oct 2007 03:58:10 +0000

[...] end of the curve, things that, yeah, can happen, but have to be pushed. For example, there’s proteasome splicing : biochemically a really cool phenomenon, that got picked up by CTL readouts — but it’s [...]

By: suicyte

suicyte — Mon, 25 Jun 2007 09:06:11 +0000

Oh, sorry if my comment was not clear. I meant to say that I don’t see two peptide joined into one, but rather two peptides converted to two other peptides. Something like this:
ABCDEFGH + uvxy -> ABCuvxy + DEFG
The resulting peptide “ABCuvxy” looks like it has been assembled from two short peptides, but isn’t.

Maybe I am completely wrong, but this mechanism would be something I can live with, while a true joining of ends would be too much of a broken dogma.

By: iayork

iayork — Mon, 25 Jun 2007 01:12:32 +0000

I donâ€™t think it is correct to speak of a â€˜reversed reactionâ€™ in this context

Well, at the end of the day, the result is the opposite — you join together two peptides and make one, instead of breaking one peptide into two. In that very general, functional sense, the reaction is going in reverse. At the molecular level, sure, it’s very unlikely that it’s literally a reverse reaction.

By: Suicyte

Suicyte — Mon, 25 Jun 2007 00:58:25 +0000

I don’t think it is correct to speak of a ‘reversed reaction’ in this context. I find it really hard to imagine that the proteasome (or any other protease) would be able to join a free peptide N-terminus to a free C-terminus.
What I consider much more likely is a mechanistic transpeptidation. During a normal hydrolysis of a peptide bond, proteases form covalent intermediates with the substrate, which are subsequently hydrolyzed by water, thus restoring the enzyme active site and liberating the cleavage products. It is conceivable that under certain conditions, hydrolysis by water can be replaced by ‘aminolysis’ performed by a primary amino group (like e.g. the N-terminus of a peptide).
This reaction is still related to a hydrolysis and can hardly be called ‘acting in reverse’.

By: Cells Weekly #34 « Migrations

Cells Weekly #34 « Migrations — Sun, 17 Jun 2007 15:52:42 +0000

[...] Peptide Splicing, Proteasomes, and Immunity [...]