Thursday, December 9, 2010

Stringent response - why are we still in the middle ages? Part I.

Bacteria grow in order to grow, this is what they do. And they try to do so as efficiently and fast as possible. This results in two things.

First, they mostly produce stuff for producing more stuff, and that would be ribosomes for making proteins. Ribosomes and other translational components (tRNAs, protein factors) constitute the bulk of  bacterial dry mass.

Tightly connected to this ribosomal expansion phenomenon is the fact that bacteria really, really need to regulate production of their so-called stable RNA (ribosomal RNA (rRNA) and tRNA (shame on me... transfer? transport? well, you get the idea!). Regulation of the stable RNAs is regulation of bacterial growth, it is that simple (really not! but let us simplify). And in order to regulate production of these RNA they have stringent response and specifically RelA protein.

In reality they have stringent response in order to cause me pain. The good thing is that they do not cause pain exclusively to me, although most of the other people who were working on stringent response have by now either moved to other fields, or nearing retirement and thus are nor so afraid of working on the stringent response any more, or died. I can not switch fields now, nor can I retire yet. Alternatives?

For all the major steps and players of translational machinery we are now enjoying massive amounts of high quality data. Structures are available, mechanisms are described as very, very detailed kinetic schemes etc. For RelA this is not the case.

We have a very, very vague idea about the mechanism and we have an x-ray structure of the truncated protein. However, we have no cryo-structure of RelA bound to the ribosome, as we have do for the majority of other translational factors (and usually in many different complexes!), nor do we have any kinetic schemes dissecting the mechanism into individual steps. All we have is bulk enzymatic assays providing Km and kcats, but this is really not in the keeping with the the advancement of our understanding of all other aspects of translation and its regulation.

Why is that so? Next time I feel like blogging, I will try addressing this question.

Mendeley group on stringent response

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