1
$\begingroup$

I try to get a picture of the life cycle of a protein (considered as a specific molecule).

This is how I can imagine it:

  1. After the cell is born a protein molecule is synthesized by gene expression for the very first time de novo. This happens at a specific point in time and in space, typically at an ribosome, which may be located anywhere inside the cell.

  2. From the location of its generation (combination or recombination, see below) the protein travels to its final destination, e.g. as an ion channel in the cell membrane. (But possibly it was already synthesized very close to its point of use.) Or it just floats around in the cytosol. (Possibly, it gathers some other biomolecules around it.)

  3. Whereever it arrives or not: the protein lives and works for some time.

  4. Eventually, it gets damaged (= looses small functional units), but gets repaired in situ. Continue with 3.

  5. Eventually, it gets marked by ubiquitin and destructed in a controlled manner. Continue with 7.

  6. Eventually, it decays spontaneously (= splits into some larger fragments).

  7. Its fragments are released (in case it was bound) and start again to float around in the cytosol.

  8. Eventually, its (or other proteins') fragments are recombined (at specific points in time and in space, possibly at "re-factories" comparable to the ribosome-"factories"). Continue with 2.

Is this rough picture of the life-cycle of a protein essentially correct?

If so: What is known about the time ranges in which these processes take place? Especially: How long is the effective life and working time of typical proteins? Are there proteins that live and work only for minutes or hours, and others that live for months or years? (Specific examples are welcome!)

$\endgroup$
  • 1
    $\begingroup$ One missing aspect (for Eukaryotes) is that step 5 is actively promoted by tagging with ubiquitin (en.wikipedia.org/wiki/Ubiquitin). You might be interested in this post biology.stackexchange.com/questions/46274/… $\endgroup$ – gilleain Nov 8 '17 at 17:16
  • $\begingroup$ Just today - after a heavy autumn storm - I saw trees in a nearby park marked (by some red-white stripes) to be felled. Is this how ubiquitin works? $\endgroup$ – Hans-Peter Stricker Nov 8 '17 at 19:21
  • $\begingroup$ @HansStricker pretty much. Proteins tagged with ubiquitin (i.e. ubiquitinated) are recognized and degraded by proteasomes. Wikipedia wouls surely give some nice info about this :) $\endgroup$ – another 'Homo sapien' Nov 8 '17 at 19:30
  • $\begingroup$ @gilleain: I added ubiquitinization in the question. Thanks for the hint. $\endgroup$ – Hans-Peter Stricker Nov 9 '17 at 11:28
3
$\begingroup$

Protein half-lives range from less than 30 min (e.g., oxidoreductases) to more than 200 hr (e.g., some nucleic-acid binding proteins) and up to, at least, 2000 hr [Rahman & Sadygov, 2017, PLoS One 12(7): e0180428].

More ubiquitination sites, shorter half-life; more/larger intrinsically disordered regions, shorter half-life; more tightly coupled with the cell cycle, shorter half-life.

Note: Not all eukaryotic proteins are degraded via the ubiquitin-proteasome proteolytic pathway.


http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180428

$\endgroup$
  • $\begingroup$ Thanks, Martin! Do you possibly know typical life times of ion channels (membrane proteins)? Or do they vary as much as for proteins in general? $\endgroup$ – Hans-Peter Stricker Nov 9 '17 at 11:25
  • $\begingroup$ Two examples (many more, i think, can be found with an ion-channel-specific literature search): BKα subunit of BK ion channel > 10 hr; Kv1.3 ion channel ~ 4 hr; Kv1.3 ion channel interacting with TrkB ~ 6.5 hr. $\endgroup$ – user37894 Nov 10 '17 at 7:18
  • $\begingroup$ This means: ion channels are in a permanent dynamic equilibrium (on a rather small time range of some hours)? Isn't that thrilling (given the fact of long-term potentation)? (This means, long-term potentation is more of an epigentic effect than the result of permanent changes of long-living ion channel proteins, isn't it? $\endgroup$ – Hans-Peter Stricker Nov 10 '17 at 7:47

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.