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I initially thought that a domain was a specific part of a protein, with it given tertiary structure, to which a given molecule is able to bind. (I think I recall phrases such as "the haem binding domain of protein X..." being used in lectures?)

Having consulted Wikipedia on protein domains, I see the definition is a bit more subtle:

A protein domain is a conserved part of a given protein sequence and (tertiary) structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded.

I can understand this, however the reason why I started questioning what a 'domain' actually refers to was because if it's use in reference to Sda in control of endosporulation of bacteria. In my lecture notes, it is stated that "KinA is bound and destabilised by Sda, a DnaA target,"

From this I was under the impression that Sda is a protein (although to the best of my knowledge DnaA only binds DNA, so I do not know why Sda would be target of DnaA. Anyhow,) on the other hand Wikipedia states "the protein domain Sda is short for suppressor of dnaA or otherwise known as sporulation inhibitor A.", which seems to me to suggest that Sda is a part of DnaA whose modifications allow DnaA suppression?

Also, on Wikipedia, it is later written "Sda protein domain is a checkpoint which prevents the formation of spores." How can a protein, if Sda is one, be a checkpoint?

On the other hand my lecture notes later talk about the regulation of Sda levels, so it again is referred to as a separate protein!

I would very much appreciate if someone could explain what 'domain' means in this context.

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    $\begingroup$ There is nothing in the idea of a domain that requires it to bind a particular molecule. The definition in Wikipedia sounds reasonable enough — domain doesn't mean anything else in a protein context. So I am unclear what your question is. Are you asking us to clarify the use of this word in a text to which you don't give a reference and may be poorly written and use words loosely? Surely not. Or are you asking us to explain a scientific description of a DNA-binding system in sporulation? If so you need to present it more clearly with references and do a little more research yourself. $\endgroup$
    – David
    Apr 21, 2017 at 15:31

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Short answer

Wikipedia has unnecessarily made an already confusing situation much worse. Sda is its own protein, it is regulated by DnaA, and it prevents sporulation.

Full answer

I don't think your misunderstanding is based on the meaning of 'domain' - the definition you give sounds quite reasonable - but rather the use of the term domain with respect to Sda and the naming of Sda itself, which I agree is quite confusing and made much worse by Wikipedia in this case.

Sda is a protein that inhibits KinA activity (Burkholder et al., 2001) and is a completely separate protein from DnaA. I don't see where you jumped from your notes to the idea that Sda is a domain of DnaA except for from Wikipedia: I don't know why Wikipedia thinks Sda is a protein domain, it is a protein. It is a very small protein, so perhaps it would be appropriate to think of it all as one domain, but there is not a single result for "Sda protein domain" on Google Scholar - no one else is using this terminology. A full Google search only returns a few (~150) results, most of which are direct copies/translations from Wikipedia, or Wikipedia is a direct copy of them. Wikipedia can be useful, but if it starts to cause you confusion, don't assume it is correct.

The phrasing "KinA is bound and destabilised by Sda, a DnaA target" means that Sda binds KinA and destabilizes it, and notes that Sda is a target of DnaA; since DnaA is a transcription factor, you can infer that this means that DnaA controls expression of Sda in some way.

In biology a checkpoint just refers to a place that a process can be halted/arrested, often in reference to the cell cycle. Sda is considered a checkpoint because when Sda is expressed, it prevents cells from sporulating by indirectly preventing activation of Spo0A (Burkholder et al., 2001).

Another source of confusion is that the name "suppressor of dnaA" on Wikipedia is WRONG, but further, molecular biologists sometimes have an impenetrable way of naming things, owing to the complexity of control of gene expression and the circuitous way that new proteins are identified and understood.

The correct name for sda is "suppressor of dnaA1". dnaA1 is NOT DnaA - dnaA1 is a MUTANT ALLELE of DnaA that results in cells that are completely unable to sporulate. But! sda is also NOT Sda: sda is a MUTANT ALLELE that produces non-functional Sda (the protein).

I'll quote from the title of the table in Burkholder et al:

sda Mutations Suppress the Sporulation Defect of dnaA1 Mutants

Or, stated again, in dnaA1 mutants, there is a defect in DnaA which prevents sporulation. The researchers searched for mutations that would reverse this effect. They found one, and named it sda, because it reverses (suppresses) the effect of the mutation they were studying. The dnaA1 mutant's effects on sporulation seem to be caused by an increased expression of Sda, which is why the sda mutant reverses the effect.

References


Burkholder, W. F., Kurtser, I., & Grossman, A. D. (2001). Replication initiation proteins regulate a developmental checkpoint in Bacillus subtilis. Cell, 104(2), 269-279.

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  • $\begingroup$ +1 at least for this: molecular biologists sometimes have an impenetrable way of naming things, though the whole answer was great. $\endgroup$
    – canadianer
    Apr 21, 2017 at 21:01
  • $\begingroup$ @canadianer Seriously, I mean come on. $\endgroup$
    – Bryan Krause
    Apr 21, 2017 at 21:56
  • $\begingroup$ Ha! That was the exact example I was thinking of as I typed that comment. $\endgroup$
    – canadianer
    Apr 21, 2017 at 21:57

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