I know that quaternary protein structures are formed exclusively via non-covalent bonds. My biochemistry professor discussed a viral capsid that is essentially one quaternary structure with 240 individual monomers of 4 kinds. I suspect that for this protein coat to be stable, the non-covalent bonds holding it together must be rather stable. He also mentioned that different monomers can join to form the functional protein complex from relatively far distances, like across an entire cell, which once again leads me to believe that both monomers must be interacting with each other very strongly.

My question is: Since a strong non-covalent interaction is required between (at least) two protein monomers to form the functional quaternary structure, can one particular protein be a monomer to an array of different quaternary complexes? Are there any examples of this?

  • $\begingroup$ I realize that this question isn't exactly "precise", and I might be using the wrong terminology. Feel free to edit or let me know how I can improve the question. $\endgroup$ May 15, 2012 at 17:48
  • 1
    $\begingroup$ Are you limiting this to protein complexes which assemble irreversibly? Otherwise anything where two proteins attach temporarily to form an active enzyme would be an example. E.g. cyclin-dependent kinase (CDK) and the different cyclins. $\endgroup$
    – Armatus
    May 15, 2012 at 18:12
  • $\begingroup$ I had originally asked this question with irreversability in mind, but just activation would make a great addition to the answer. $\endgroup$ May 15, 2012 at 18:42
  • $\begingroup$ I would say that there are quite a few quaternary protein structures that are connected by intermolecular cystine bonds. $\endgroup$
    – bobthejoe
    May 22, 2012 at 6:55

1 Answer 1


If I understand the question correctly, you're thinking something along the lines of modular tertiary domains, but in a quaternary sense?

For a reversible interaction, heterotrimeric G proteins spring to mind. Once activated by a G protein coupled receptor (GPCR), the alpha subunit and the beta-gamma complex dissociate from the receptor and from each other. They can both go on to affect signaling by binding to various effector proteins, depending on the particular pathway in which they are involved, and their activities can be mediated by other proteins (e.g. the alpha subunit GTPase regulated by GAP proteins).

I spoke to my Protein Engineering professor, and she also directed me to a few examples, although I'm not sure they're quite what you're looking for in the strictest sense.

  • Cyclin-dependent kinases, as @Armatus mentioned, bind to all sorts of different cyclins. (I get the sense that subunits found in multiple protein complexes will probably be more common in signal cascades. I don't have any real data on that, but it makes sense that a signal protein could interact with two or more protein complexes and even have slightly different functions in each.)
  • Alcohol dehydrogenase (ADH) is an example of a protein with different quaternary structures between species. According to my professor, it occurs as a homodimer in mammals, but as a tetramer with some slightly different residues in budding yeast. I can't say whether the sequence changes are what affect the oligomerization, although my prof also mentioned "oligomerization domains" that could mediate protein-protein interactions.
  • She also directed me toward a slightly more interesting example (in my opinion), though, again, it's also more along the lines of oligomerization. Small heat shock proteins (sHSPs) undergo something called "dynamic subunit exchange" and can take on a wide variety of oligomeric architectures. Binding is transient, but it's still kind of neat. There's a review here: http://www.sciencedirect.com/science/article/pii/S0968000411001903. Figure 3 shows different oligomeric architectures from the one monomer.

It seems that pretty much any protein that interacts with two or more separate protein complexes could be considered an answer. Neither I nor my professor have managed to come up with an example of an irreversible assembly of common subunits, but she is of the opinion that, in all the different possible protein structures, there is probably at least one example of everything, no matter how outlandish it seems.


You must log in to answer this question.

Not the answer you're looking for? Browse other questions tagged .