Another weird experiment (Altius 9 #55 Bio)

[salemstein]

I'm not buying C as the right answer, though I could totally be wrong. I think the correct answer (not listed in any answer choice) is that phosphorylation of either S451 or S462 is required and sufficient for activation. If you look at the passage, IRF5 gets shut down completely only when both S451 and S462 get dephosphorylated (same thing cuz they changed it to Alanine). But, even if only one of the sites got phosphorylated, the gene is still activated, albeit at a lower rate. The only way C would be correct is if you assume by "activation" you need 100% activation, but theres no way I can glean that from the Q stem.

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[wizzed101]

It depends really. If the gene is haploinsufficient at less than say 90% of the wild-type dosage, both sites will be required. I don't see that info though.

 

[salemstein]

Yea, the sufficiency rates are at 30% and 95% of WT for 462 and 451 haplo-substitutions. Paragraph 1 (couldn't copy due to space) only had some random background info. No graphs this passage

 

[theonlytycrane]

Copy the whole passage? I'm interested now

 

[salemstein]

Copy the whole passage? I'm interested now

Here it is, no pic or graphs on original:

Primary protein structure is of precise biofunctional importance in living systems. Single amino-acid substitutions or deletions are known to cause many chronic disease conditions. A large number of biosignaling pathways and receptor binding interactions are functionally dependent on one or a few amino acid residues.

In a recent study, investigators examined the activation of the immunoregulatory transcription factor Interferon Regulatory Factor 5 (IRF5). IRF5 was known to be activated, to varying degrees, by several regulatory factors and proteins that are part of the innate immunity cascade. These activators are functionally similar in that they allphosphorylate serine residueson IRF5. Researchers sought to determine whether phosphorylation of these residues was required or sufficient for IRF5 activation.

Two serine residues, S451 and S462, had been demonstrated by previous studies to be important to IRF5 activation. Phosphomimetics are specialized amino acid residues that mimicin vivophosphorylation when substituted for an existing amino acid. To further elucidate their function,alanine loss-of-function and aspartic acid phosphomimetic substitutions were tested. The most significant effect was found with the S462A substitution. This single mutation reduced transcriptional induction of IRF5 by 70% compared to wild-type IRF5. The S451A substitution reduced induction of IRF5 by 5%. The double mutation SS451,462AAterminatedassay-detectable IRF5 function. Each mutation condition was examined in multiple trials in the presence and absence of all possible combinations of seven known innate immunity cascade modulators and the same functional reductions were observed for alanine-substituted IRF5. Following data collection, phosphomimetic Asp substitutions were performed on the same cell lines, resulting in upregulation of IRF5 activity in all cases. In a follow-up experiment, IRF5 mutants that lack serines 451 and 462 were demonstrated to be unable to induce IRF5 gene expression.

 

[theonlytycrane]

@salemstein thanks for posting!

I agree with you about their implicit requirement of 100% for activation. I think there should be some qualifying information (or maybe there are values that I am not aware of). If I make up random values: let's say that 70% transcriptional induction still results in normal function. With that said, S451 would be required and sufficient because even with knocking S462 out we will get the 70%.