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Proteins are defying textbooks

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We bet this isn’t the only time they have done so. 😉

Here, from U Utah Healthcare:

Open any introductory biology textbook and one of the first things you’ll learn is that our DNA spells out the instructions for making proteins, tiny machines that do much of the work in our body’s cells. Results from a study published on Jan. 2 in Science defy textbook science, showing for the first time that the building blocks of a protein, called amino acids, can be assembled without blueprints – DNA and an intermediate template called messenger RNA (mRNA). A team of researchers has observed a case in which another protein specifies which amino acids are added.

“This surprising discovery reflects how incomplete our understanding of biology is,” says first author Peter Shen, Ph.D., a postdoctoral fellow in biochemistry at the University of Utah. “Nature is capable of more than we realize.”

To put the new finding into perspective, it might help to think of the cell as a well-run factory. Ribosomes are machines on a protein assembly line, linking together amino acids in an order specified by the genetic code. When something goes wrong, the ribosome can stall, and a quality control crew is summoned to the site. To clean up the mess, the ribosome is disassembled, the blueprint is discarded, and the partly made protein is recycled.

Yet this study reveals a surprising role for one member of the quality control team, a protein conserved from yeast to man named Rqc2. More.

But what is this about “Nature is capable of more than we realize”? Does nature have a mind that has a search space for solutions?

Like a half-made car with extra horns and wheels tacked to one end, a truncated protein with an apparently random sequence of alanines and threonines looks strange, and probably doesn’t work normally. But the nonsensical sequence likely serves specific purposes. The code could signal that the partial protein must be destroyed, or it could be part of a test to see whether the ribosome is working properly. Evidence suggests that either or both of these processes could be faulty in neurodegenerative diseases such as Alzheimer’s, Amyotrophic lateral sclerosis (ALS), or Huntington’s.

“There are many interesting implications of this work and none of them would have been possible if we didn’t follow our curiosity,” says Brandman. “The primary driver of discovery has been exploring what you see, and that’s what we did. There will never be a substitute for that.”

Are these people trying to say, don’t fire us because we find evidence for design in nature?

If so, let’s hope they are not forced to yelp some fake disclaimer at a press conference.

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Comments
Concerted Action of the Ribosome and the Associated Chaperone Trigger Factor Confines Nascent Polypeptide Folding DOI: http://dx.doi.org/10.1016/j.molcel.2012.07.018 How nascent polypeptides emerging from ribosomes fold into functional structures is poorly understood. http://www.cell.com/molecular-cell/abstract/S1097-2765(12)00645-4Dionisio
January 16, 2015
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Quality control of a cytoplasmic protein complex: Chaperone motors and the ubiquitin-proteasome system govern the fate of orphan fatty acid synthase subunit Fas2 of yeast doi: 10.1074/jbc.M114.596064 For the assembly of protein complexes in the cell the presence of stoichiometric amounts of the respective protein subunits is of utmost importance. A surplus of any of the subunits may trigger unspecific and harmful protein interactions and has to be avoided. A stoichiometric amount of subunits must finally be reached via transcriptional, translational and/or post-translational regulation. http://www.jbc.org/content/early/2015/01/06/jbc.M114.596064Dionisio
January 16, 2015
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The Hsp90 Cochaperones Cpr6, Cpr7, and Cns1 Interact with the Intact Ribosome doi: 10.1128/EC.00170-14 The abundant molecular chaperone Hsp90 is essential for the folding and stabilization of hundreds of distinct client proteins. Hsp90 is assisted by multiple cochaperones that modulate Hsp90's ATPase activity and/or promote client interaction, but the in vivo functions of many of these cochaperones are largely unknown. http://ec.asm.org/content/14/1/55.abstractDionisio
January 16, 2015
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DNA_Jock Again, I have to admit it: Ty umnitsa, prosto molodets! :)Dionisio
January 16, 2015
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DNA_Jock Would you mind to explain why you are so afraid to answer such easy questions, which just require a little online search? Maybe your comrade AVS hasn't responded yet because he's on vacation or out of town? But you can't use those excuses, because you're still writing in this blog.Dionisio
January 16, 2015
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DNA_Jock Of course your comrades will always agree with you at the end, because y'all respond to a common party line. :) Don't worry about answering the questions I asked AVS (apparently he had not answered yet). The answers are most probably in the same paper or in other papers. Just have to locate and highlight them. I'm not specially interested in those answers at this point, because they won't make a difference in the current phase of my project, which has to do with the proof of concept for the approach I use in order to organize the gathered papers online. Perhaps later some potential users of the method might be interested in having those particular questions answered. They'll figure out a way to obtain the info they want. Rest assured that they won't need your help for that. :)Dionisio
January 16, 2015
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LMAO, Dionisio. Did you notice my response to hrun0815 at #144, i.e. the next post?
hrun, I would like Dionisio to confirm the specific URL that he used to copy the text he used in 107. If it was the pubmed link he provided in that post, then answering will be really easy…
Really easy, and yet you seem strangely reluctant to answer. Curious that. Notice also my explicit acknowledgement that you did provide a link to pubmed, making your 166 and 173 look kinda dumb. hrun0815 understood my explanation @144, but he did not understand why you refused to respond, saying @148
What prevented Dio from just C/P the PubMed link from 107 and then get the answers he was supposedly looking for? And even if he was not actually looking for those answers, why not just C/P and pretend that you are? Why repeat the endless description of his paper collection process?
He did understand my 'reveal' @161 too, responding
Well spotted, DNA_Jock. Well spotted.
So I'm quite confident that hrun0815, along with anyone else with the stamina to wade through your spam, understands just fine. Or they could just read #161. You couldn’t make this stuff up. Indeed.DNA_Jock
January 16, 2015
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DNA_Jock Since your buddy hrun0815 has been so ineffective* in helping you, maybe other comrades and fellow travelers could give it a try too? wouldn't you invite them to step in and give you a hand? :) (*) even your buddy hrun0815 publicly admitted that he didn't understand your senseless request. Here's what he wrote to you in his post #143:
I don’t understand. I believe he [Dionisio] did provide the URL. The quote is taken directly from PubMed (or PLOS or PMC). Did you [DNA_Jock] mean a different post?
Dionisio
January 16, 2015
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Dionisio: You know very well that the link to the referred paper was provided in my post #107.
And I have never, ever written anything to suggest otherwise.
The information you requested is available to anyone who read my post #107 (until the last time I verified it).
Just as wrong as the last time you said it. I have been asking you to provide the URL from which you extracted the text that you pasted into post 107. If that link is where you copied the text from, then all you need to do is say so. Let me rephrase it, in case you still didn’t understand it well: Was the text in post 107 copied from the web page linked to in post 107? If not, then where was it copied from?
Your request was completely unnecessary, therefore your complaints are unjustifiable.
You can read 161 for an explanation of the motivation behind my offer. I am not complaining at all. More like pointing and laughing, I'm afraid.DNA_Jock
January 16, 2015
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Is it possible that some interlocutors in this blog are cover agents, hired to entertain the rest of us, pretending to say obnoxious things, just to provoke more heated debates, which supposedly may increase the visitors count and the number of registered commenters? That idea seems a little senseless, but who knows?Dionisio
January 16, 2015
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DNA_Jock Let me rephrase it, in case you still didn't understand it well: You know very well that the link to the referred paper was provided in my post #107. The information you requested is available to anyone who read my post #107 (until the last time I verified it). Your request was completely unnecessary, therefore your complaints are unjustifiable. No idea why you made such a big deal out of that. Nice try, but it failed. Try better next time. :) :)Dionisio
January 16, 2015
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#167 DNA_Jock
Not quite sure what that means.
Sorry, there was a huge grammar mistake, that most certainly rendered my statement totally unintelligible. Let me correct it for you: "Specially if you don’t know the answers, but that is not your case, is it?" Is that more clear now? :)Dionisio
January 16, 2015
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Wow, those are interesting questions. What do you think the answers are?DNA_Jock
January 16, 2015
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DNA_Jock Ty umnitsa, prosto molodets! :) PS. I recall someone suggested a while ago that some of the interlocutors here in this blog could be cover agents working for the blog owners, constantly saying obnoxious things in order to test some of the frequent commenters. Could that be possible? That idea doesn't make much sense, but who knows? :)Dionisio
January 16, 2015
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#166 addendum DNA_Jock Which of these cases contributed more to your decision? 1. Post #162? 2. Post #164? 3. Both posts combined? 4. None of the above? 5. Something else? Please specify______ (optional) Just having fun here... :)Dionisio
January 16, 2015
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Hrun0815
Still, the whole charade seems puzzling to me.
It’s a game of “Why don’t you/Yes but”. The Berne-approved game-breaking response is “Wow, that is an interesting question. What do you think the answer is?, which seems justified at this stage. Eagerness to play this game implies a failure to move out of the “I’m not OK” life-stage. Oh well.DNA_Jock
January 16, 2015
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Oh, Dionisio,
#165 DNA_Jock Does that mean that you’re willing to leave my questions publicly unanswered in this forum? If that’s your choice, it should be respected.
How nice of you.
No one has the right to make you answer any questions here.
I agree with you, but you might want to let Barry know (LNC, anyone?) (ggg)
Specially if you don’t know the answers, which it’s not your case, right? Have a good weekend. O.
Not quite sure what that means.
PS. You know very well that the link to the referred paper was provided in my post. The information you wanted was available to anyone who read my post.
Wrong, Dionisio. You still have not stipulated the source of the text that you cut and pasted. Please re-read my offer carefully.
Your request was part of your agenda in this blog. Don’t pretend to be so innocent now.
My offer was designed to present you with a dilemma, as I explained quite openly to hrun0815 in 161. So far, you have managed to impale yourself on both horns. That’s quite the feat.
Nice try, but it failed.
Au contraire, mon petit ami, au contraireDNA_Jock
January 16, 2015
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#165 DNA_Jock Does that mean that you're willing to leave my questions publicly unanswered in this forum? If that's your choice, it should be respected. No one has the right to make you answer any questions here. Specially if you don't know the answers, which it's not your case, right? :) Have a good weekend. O. PS. You know very well that the link to the referred paper was provided in my post. The information you wanted was available to anyone who read my post. Your request was part of your agenda in this blog. Don't pretend to be so innocent now. Nice try, but it failed. :)Dionisio
January 16, 2015
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Dionisio, My offer, originally made @140, still stands:
Dionisio,
when is Nat10 produced for the case of the discussed paper? what triggers that gene expression in relation to the discussed paper? what amount? or is it produced constantly? or is it produced for other processes and just happen to be available for the discussed process too?
I have an offer for you. I will provide the answers (including references) to these questions for free, if you first provide the URL for the text that you pasted into comment 107.
[Emphasis added] For additional questions, my usual consulting rates will apply. As has been noted elsewhere, you may find engaging a collaborator more cost-effective.DNA_Jock
January 16, 2015
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#162 addendum Please, be aware that the information you provide may trigger newer questions. Basically, you may think like a systems analyst trying to write programming specs. I will be playing the role of a programmer trying to understand the detailed tech specs you write. Thank you.Dionisio
January 16, 2015
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You couldn’t make this stuff up. Really.
Well spotted, DNA_Jock. Well spotted. I simply put Dio's posts that refer to published work in my mental TL;DR category (which is getting more and more crowded here on UD). With this it is also much easier to understand Dio's disdain in getting some information how to effectively run a project like the one he claims to be working on. Clearly there is no honest interest in the underlying science (considering the multiple points raised by me and others) nor in how to effectively build software relevant to biology. Still, the whole charade seems puzzling to me.hrun0815
January 16, 2015
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#161 DNA_Jock Can you answer my questions in posts #129-133 and 137-138? Remember, don't leave any potential questions unanswered, at any level of details, because the unanswered questions might come back to you like boomerangs. Please, note that if your answer includes references to papers, please, quote the text that answers my questions, providing the page number where that text is located within the given document. Thank you.Dionisio
January 16, 2015
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Hrun0815, As Dionisio has gone all Lobster Thermidor, I will explain why I expected him to find my offer unappealing. Dionisio’s original post @107
RNA cytidine acetyltransferase of small-subunit ribosomal RNA doi: 10.1371/journal.pone.0112156. The eukaryotic small-subunit (SSU) ribosomal RNA (rRNA) has two evolutionarily conserved acetylcytidines. However,the acetylation sites and the acetyltransferase responsible for the acetylation have not been identified. http://www.ncbi.nlm.nih.gov/pubmed/25402480
AVS asked him why he highlights particular phrases in his C&P’s. He replied @118
AVS,
Why do you highlight certain statements such as “the acetylation sites and the acetyltransferase responsible for the acetylation have not been identified?”
Ok, that’s a valid question. I try and highlight some of the issues that are not explained in the given paper, but may be described in other papers or might be explained in future papers soon. This is kind of like a reminder, so that I keep an eye on the given subjects, in order to detect any information that may pop up in another paper and shed more light on some of the issues that currently are poorly described.
Now, I was fairly confident that Dionisio’s source for the text he pasted included the full title of the article, which is “RNA cytidine acetyltransferase of small-subunit ribosomal RNA: identification of acetylation sites and the responsible acetyltransferase in fission yeast, Schizosaccharomyces pombe.” Thus Dionisio, by revealing the source of his text, would be admitting that he went to the effort of separating the colon from the “RNA” when he carefully deleted the second half of the title “: identification of acetylation sites and the responsible acetyltransferase in fission yeast, Schizosaccharomyces pombe.” And then bolded this phrase from the abstract “the acetylation sites and the acetyltransferase responsible for the acetylation have not been identified.” because it was one of the “issues that are not explained in the given paper”. That's pretty blatant... Now, I cannot know whether Dionisio realized that this specific point was where I was heading, or whether he merely suspected a trap. Given that he is not actually interested in getting his questions answered, merely in posing them for rhetorical effect, I was confident he would find my offer unattractive. As AVS noted, Dionisio’s technique is quite transparent. Here’s another fun example: Dionisio @105
Structural basis for diversity in the SAM clan of riboswitches. doi: 10.1073/pnas.1312918111 In bacteria, sulfur metabolism is regulated in part by seven known families of riboswitches that bind S-adenosyl-l-methionine (SAM). Direct binding of SAM to these mRNA regulatory elements governs a downstream secondary structural switch that communicates with the transcriptional and/or translational expression machinery. The most widely distributed SAM-binding riboswitches belong to the SAM clan, comprising three families that share a common SAM-binding core but differ radically in their peripheral architecture. Although the structure of the SAM-I member of this clan has been extensively studied, how the alternative peripheral architecture of the other families supports the common SAM-binding core remains unknown. http://www.ncbi.nlm.nih.gov/pubmed/24753586
Cool, so one of Dio’s “issues that are not explained in the given paper” is “how the alternative peripheral architecture of the other families supports the common SAM-binding core remains unknown”. The sentence immediately following the one he bolded reads
We have therefore solved the X-ray structure of a member of the SAM-I/IV family containing the alternative "PK-2" subdomain shared with the SAM-IV family.
You couldn’t make this stuff up. Really.DNA_Jock
January 13, 2015
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Posttranslational modification of Sirt6 activity by peroxynitrite doi:10.1016/j.freeradbiomed.2014.11.011 http://www.sciencedirect.com/science/article/pii/S0891584914013744Dionisio
January 11, 2015
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Post-translational modifications are the chemical modifications of proteins subsequent to their biosynthesis. The modification of certain amino acid residues may result in changes of the protein conformation and/or its capacity to interact with other proteins or ligands, to be active or inactive in the case of an enzyme, to allow or interfere with gene expression and many other biological functions. http://www.biosyn.com/tew/protein-post-translational-modifications.aspx?_escaped_fragment_=
Dionisio
January 11, 2015
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Post-translational modifications: SUMO size me doi:10.1038/nchembio.1674 The reversible attachment of small ubiquitin-like modifier (SUMO) proteins to the lysine side chains of specific proteins is necessary for genome stability and transcription. http://www.nature.com/nchembio/journal/v10/n11/full/nchembio.1674.html
Dionisio
January 11, 2015
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Alternate deacylating specificities of the archaeal sirtuins Sir2Af1 and Sir2Af2 doi: 10.1002/pro.2546. Sirtuins were originally shown to regulate a wide array of biological processes such as transcription, genomic stability, and metabolism by catalyzing the NAD(+) -dependent deacetylation of lysine residues. Recent proteomic studies have revealed a much wider array of lysine acyl modifications in vivo than was previously known, which has prompted a reevaluation of sirtuin substrate specificity. Several sirtuins have now been shown to preferentially remove propionyl, succinyl, and long-chain fatty acyl groups from lysines, which has changed our understanding of sirtuin biology. In light of these developments, we revisited the acyl specificity of several well-studied archaeal and bacterial sirtuins. We find that the Archaeoglobus fulgidus sirtuins, Sir2Af1 and Sir2Af2, preferentially remove succinyl and myristoyl groups, respectively. Crystal structures of Sir2Af1 bound to a succinylated peptide and Sir2Af2 bound to a myristoylated peptide show how the active site of each enzyme accommodates a noncanonical acyl chain. As compared to its structure in complex with an acetylated peptide, Sir2Af2 undergoes a conformational change that expands the active site to accommodate the myristoyl group. These findings point to both structural and biochemical plasticity in sirtuin active sites and provide further evidence that sirtuins from all three domains of life catalyze noncanonical deacylation. http://www.ncbi.nlm.nih.gov/pubmed/25200501
Dionisio
January 11, 2015
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Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. doi: 10.1016/j.cmet.2014.03.014. We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (Kglu). http://www.ncbi.nlm.nih.gov/pubmed/24703693
Dionisio
January 11, 2015
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Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation doi: 10.15252/msb.20145524. Ribosome profiling data report on the distribution of translating ribosomes, at steady-state, with codon-level resolution. http://www.ncbi.nlm.nih.gov/pubmed/25538139
Dionisio
January 11, 2015
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In silico prediction of structure and functions for some proteins of male-specific region of the human Y chromosome. doi: 10.1007/s12539-013-0178-5 [...] The results of these structure-functional annotations provide a comprehensive view of the proteins encoded by MSY, which sheds light on their biological functions and molecular mechanisms. [...] http://www.ncbi.nlm.nih.gov/pubmed/24402818
Dionisio
January 11, 2015
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