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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
AVS: Well, at least we agree on something at last. I don't agree that "The only thing that matters is hydrophobic content". Have you evidence of that? I don't know where you get the "likely alpha helix structure as well in the CAT tail" concept. However, nothing of that is really important. I don't understand why you say:
“So, no specific information added here by the protein, except for a “signal” that means: this is a defective protein.” Is the equivalent of saying “I never get into car accidents, except for when I get into a car accident” That’s the lawyer doublespeak you seem to do so well.
Maybe my English is really poor, but I believed that saying: "no specific information added except for a signal that means so and so" simply means that the signal information is added, and no other information. Is that doublespeak? The example of accidents is not appropriate. The protein could well add the information which represents the signal (a random sequence of alanine and threonine) and other information, for example a specific sequence with some other biochemical activity. So, I believe that my statement has a very clear meaning, and is not doublespeak. You are free to believe differently. However, I still consider the lawyer matter as a strange form of compliment. :) Deciding how similar the two things are, at this point, is a very subjective issue. I will be happy to keep my opinion, and to respect yours. And I am happy that you agree that mahuna was off the mark. Which was the only motivation of my initial post.gpuccio
January 9, 2015
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Gpuc, I’m glad you have changed your mind, from “No, there is no template” to “there is at least some form of template function.” “My point is only that in no way it determines the exact final sequence, like mRNA does.” What would you say determines the final sequence of the CAT tail then? The sequence in a single specific signal peptide is not random; obviously it is encoded in the original gene. But there is no specific sequence of signal peptides; they are random in the same sense that the sequence of alanine and threonine are random in the CAT tail. The only thing that matters is hydrophobic content and formation of an alpha helix in the signal peptide versus alanine-threonine content and a likely alpha helix structure as well in the CAT tail. “your assumption that the sequence specificity in signal peptides is completely useless, and that any bunch of “largely hydrophobic” amino acids will do the trick is completely gratuitous and unwarranted.” No, it is completely true. There is no specific sequence motif associated with the signal peptide. Its only requirement is a hydrophobic stretch of amino acids, it can be of different length and sequence. “However, protein is not adding specific sequence information, like the mRNA.” mRNA and the Rqc2 protein direct the addition of very specific amino acids. mRNA does so, according to association with tRNA molelcues as does Rqc2. They perform the same function, but in different ways. “So, no specific information added here by the protein, except for a “signal” that means: this is a defective protein.” Is the equivalent of saying “I never get into car accidents, except for when I get into a car accident” That’s the lawyer doublespeak you seem to do so well. “while the Rqc2 protein does nothing like that,” “they are two completely different things.” But they do very similar things. It’s not an exact sequence, but Rqc2 produces a peptide that results in a specific function. They are very similar. Yes mahuna was off the mark with that statement. Way off.AVS
January 9, 2015
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Oh, and by the way:
There are papers that discuss the improbability of predicting a protein’s shape given its amino acid sequence.
is not equivalent to claiming that the amino acid sequence does not determine the protein's structure or function.hrun0815
January 9, 2015
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Joe earlier:
Genetic engineers have taken the genes that encode for functional proteins in one organism and spliced them into another species only to observe the resulting polypeptide not take shape and function.
Joe when confronted with the fact that in general mammalian proteins are expressed in bacteria to be crystallized in order to examine their native structure and with it their function:
OK so that supports what I thought...
hrun0815
January 9, 2015
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#78 Aurelio Smith Can a document with over half of the authors from Hispanic background be reliable? :)Dionisio
January 9, 2015
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Mammalian proteins that are crystallized are generally not expressed in their native host tissue
And?
Currently, the vast majority of crystallized proteins are expressed in bacteria. In cases where bacteria do not express the protein correctly, insect cell suspensions are generally the next best option.
OK so that supports what I thought- bacteria and insects are live hosts. Aurelio thinks they are synthesized.
Also, Joe, since you suggest that it is not, in fact, amino-acid sequence that generally determines protein structure and function,
1- It isn't just me. There are papers that discuss the improbability of predicting a protein's shape given its amino acid sequence. 2- "generally determines" is too broad.
is it your contention that a protein with the same sequence in two different organisms has in fact a different structure and/or function in these two organisms?
NoJoe
January 9, 2015
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Why can’t scientists crystallize proteins that they remove from live hosts?
And more DK-effects here. Mammalian proteins that are crystallized are generally not expressed in their native host tissue. Currently, the vast majority of crystallized proteins are expressed in bacteria. In cases where bacteria do not express the protein correctly, insect cell suspensions are generally the next best option. Also, Joe, since you suggest that it is not, in fact, amino-acid sequence that generally determines protein structure and function, is it your contention that a protein with the same sequence in two different organisms has in fact a different structure and/or function in these two organisms?hrun0815
January 9, 2015
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Aurelio Smith- Am I supposed to guess the relevance of your links? Could you please make a case so it can be scrutinized?
Just occurs to me, Joe. How is it possible to crystallise proteins (as was done to elucidate the 3D structure of haemoglobin using X-ray crystallography) if they need chaperones to fold consistently?
Just occurs to me, Aurelio. Why don't you respond to what I actually post instead of what you think I posted? Why can't scientists crystallize proteins that they remove from live hosts?Joe
January 9, 2015
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Darwin would be 209, yet people use him as great authority... [citation needed]. Many of Darwins ideas are indeed removed from modern science, which kind of proves the point that he's not considered an authority. Only those bits of Darwin's thinking supported by subsequent science are part of today's evolutionary biology. (We talk about natural selection, we don't talk about pangenes).wd400
January 9, 2015
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Aurelio "Sermonti must be 94.Perhaps he’s not familiar with the current state of affairs in commercial biochemistry..." Darwin would be 209, yet people use him as great authority. Imagine how much his ideas are far removed of the modern affairs in science.Eugen
January 9, 2015
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So no answers to my questions, then- got itJoe
January 9, 2015
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What is the largest that blind and unguided processes are known to produce- that is without a cell nor its machinery? :razz: Yarus, et al., did some work in that regard- what did they achieve? And how would you get from a small protein that doesn't require any help to larger proteins that do? You just can't keep adding on to a functional sequence like it's a stalagmite.Joe
January 9, 2015
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In vitro protein synthesis is routine.
OK. What does that have to do with what I said? Dr Sermonti wasn't talking about ALL proteins. The proteins that require chaperones, which are the bulk of proteins used in/by organisms, won't find a functional shape without those chaperones. Human insulin is what, 51 amino acids- it doesn't need any help to fold. Long proteins- amino acid wise- are the norm. They do not play by your rules.Joe
January 9, 2015
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AGAIN: Genetic engineers have taken the genes that encode for functional proteins in one organism and spliced them into another species only to observe the resulting polypeptide not take shape and function. Dr Sermonti mentions this in the book “Why Is A Fly Not A Horse?”. If the protein’s shape was determined by the AA sequence that should not happen.Joe
January 9, 2015
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You’re mixed up between genes and proteins.
No
Genes may code for proteins.
Yes
Splicing in genes is a way of producing proteins.
Some work while most do not form.
Insulin is produced industrially using genetically engineered bacteria.
Yes, insulin is one of the few that worked. Most others did not.
I see you googled Anfinen’s dogma.
Nope, you see something that never happened.Joe
January 9, 2015
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Prions are proteins that when they contact another (sister) protein they change its shape. That shouldn't be able to happen if the AA sequence determines the shape.Joe
January 9, 2015
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But that has nothing to do with the point that a particular amino acid sequence at a particular pH and temperature will fold to a particular conformation,
It won't/ may not fold at all and I never said chaperones add function.Joe
January 9, 2015
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Genetic engineers have taken the genes that encode for functional proteins in one organism and spliced them into another species only to observe the resulting polypeptide not take shape and function. Dr Sermonti mentions this in the book "Why Is A Fly Not A Horse?". If the protein's shape was determined by the AA sequence that should not happen.Joe
January 9, 2015
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So when you wrote “that is incorrect” what were you referring to?
LoL! I was referring to what you wrote and I explained it. Did you not understand what I posted- the part after "That is incorrect"?Joe
January 9, 2015
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Are you claiming chaperones can change the properties of a protein rather than facilitate folding and prevent tangling?
How did you get that from what I posted?
Regarding the way a protein molecule is synthesised, you must think sodium chloride from natural sea salt differs in chemical properties from that made in a lab.
Obviously you are deluded. Strange that you can't actually make a case and have to rely on innuendo based on your misconceptions.Joe
January 9, 2015
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Somebody else try. I give up. If the earlier posts were not sufficient to explain it then I doubt anything I post from now on will do the trick.hrun0815
January 9, 2015
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hrun015 So final form and assembled is not the same thing? Assembled fit together the separate component parts of (a machine or other object). "my new machine is being assembled and my old one dismantled" synonyms: construct, build, fabricate, manufacture, erect, set up, join up, fit together, put together, piece together, connect, join, unite, patch up, sew (up) "how to assemble the kite" So saying final form is not the same as assembled? Is that what you're arguing about?Andre
January 9, 2015
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Protein function and final form is fully determined by the sequence of constituent amino acids (whether the protein was translated from mRNA, synthesized in vitro or from random assembly)
That is incorrect. Genetic engineers have spliced coding sequences into foreign hosts with very little success- that is only a few sequences actually made it to a functioning protein with most failing to find a functional form. Dr Sermonti mentions this in "Why Is a Fly Not A Horse?"
Leaving aside chaperones, the sequence determines the folding and any enzymic activity or other useful property that protein might have.
LoL! As if we can "leave aside chaperones" which help facilitate the folding of long polypeptides.Joe
January 9, 2015
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Please do pray tell how that makes a difference to what I've been trying to say about Dr Wells predicting it and these researchers confirming it? I'm curious......Andre
January 9, 2015
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Andre, this is my last reply to you. You are willfully ignorant, stubborn, unable to read but convinced that you are smart and knowledgable. "proteins did not need blueprints for final form or function" is not the same as "the building blocks of a protein, called amino acids, can be assembled without blueprints"hrun0815
January 9, 2015
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hrun0815 Riiiggght you said;
Andre, these researchers did not show, nor did they claim to show “that proteins did not need blueprints for final form or function” FOR THE FIRST TIME.
When they say.......... and I quote!
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
They are liars for Jesus then?Andre
January 9, 2015
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AVS: Just to be clear: "If you don’t think that Rqc2 doesn’t serve some form of a template function than you are simply being stubborn." It depends only on what you mean by "some form of template function", which seems to be a very vague definition. If you mean only that the protein constrains the sequence to two aminoacids, and attachs it in the right place and to the right protein, that is certainly true. My point is only that in no way it determines the exact final sequence, like mRNA does. Which is certainly true. "The CAT tails are not “generated without any sequence information,” the sequence information is in the Rqc2 protein and its addition of only two amino acids. This means the sequence will be made up only of these two residues.." Whoever denied that? "...and is analogous to the random, yet largely hydrophobic, sequence in signal peptides." This is false. In what sense is it similar? OK, they are made of aminoacids. Alanine is hydrophobic, but threonine is polar. And the sequence in signal peptides is not random at all. Where did you take that strange idea? The sequence is exactly coded in the genes. Are you saying that the genes are random? Moreover, your assumption that the sequence specificity in signal peptides is completely useless, and that any bunch of "largely idrophobic" aminoacids will do the trick is completely gratuitous and unwarranted. "Because, in fact, the protein in question does add specific information; the information necessary to activate the heat shock response, and it does so by adding a random sequence made up of two amino acids. Is the fact that this random sequence has a functional effect, what you don’t like?" Absolutely not! Why should I "not like" that simple fact? Of course the protein is adding specific information. Whoever denied that? However, protein is not adding specific sequence information, like the mRNA. This is the difference. So, it seems that we absolutely agree that the protein adds information, in the form of the constraint to those two aminoacids, and in the form of the correct attachment of such a signal to the right protein, so that it may be recognized. How can you think that I don't like that concept, when I stated clearly from the beginning (post #5): "So, no specific information added here by the protein, except for a “signal” that means: this is a defective protein." What is not clear in the word "except"? Why in the world do you think that I don't like the idea that a random CAT tail, made of the right two aminoacids, and attached at the right target, is not information? Who called that a "signal"? My point is simply, and always has been, that there is no coded information for a specific sequence that guides the activity of the Rqc2 protein. That activity is only constrained by what the protein can do, and the protein acts always in the same way, so that the differences in the final CAT tails are random. Whatever system has to recognize that signal, must recognize that type of signal. My point is simply, and always has been, that mRNA is all another thing, because it conveys information for an exact sequence, an information which is symbolically coded and therefore transmittable in the genes, while the Rqc2 protein does nothing like that. My point is simply, and always has been, that they are two completely different things, and that mahuna was expressing a misleading concept when he said: "You just admitted that amino acids can be assembled into genes without DNA or RNA existing first." (emphasis added) The working of the Rqc2 protein has nothing to do with genes and with heritable information (except, again, for the information in the protein structure itself, which obviously comes from a gene, and was translated by an mRNA).gpuccio
January 9, 2015
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Andre, these researchers did not show, nor did they claim to show "that proteins did not need blueprints for final form or function" FOR THE FIRST TIME. They'd be idiots if they did since this fact has been known for over sixty years. even a high school student who took biology is probably aware of this. Try and figure out what they actually claim to have shown FOR THE FIRST TIME. You are displaying a bizarre mixture of the Dunning-Kruger effect, the inability to read accurately what they are claiming, and a pigheaded stubbornness.hrun0815
January 8, 2015
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WD400 For the last time, I'm not arguing about what they do, I'm saying Dr. Wells said that proteins did not need blueprints for final form or function, these researchers showed it for the first time. Get it? Good!Andre
January 8, 2015
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Saying each signal sequence has a specific sequence is the same as saying that each finished CAT sequence has a specific sequence. In both peptides, the exact sequence does not matter, it is the overall structure and biochemical properties that matter. There is no specific sequence motif for either. In fact, there’s a pretty good chance that the CAT tails form an alpha helix as well. And now we bring up the variations of the signal sequence in a huge wiki quote, great. We are talking about the ability of the signal sequence to localize the nascent chain to the ER, the short positively charged stretch is for proteins that remain embedded in the membrane and the cleavage sight some proteins have is unimportant to this discussion. I am not denying the fact that the signal sequence is encoded in the genome and the CAT sequence is not (I said this in post 33). If you don’t think that Rqc2 doesn’t serve some form of a template function than you are simply being stubborn. The CAT tails are not “generated without any sequence information,” the sequence information is in the Rqc2 protein and its addition of only two amino acids. This means the sequence will be made up only of these two residues and is analogous to the random, yet largely hydrophobic, sequence in signal peptides. I am in no way interested in a proteins first revival I am just trying to sort out your original statement that there is “no specific information added here by the protein, except for a “signal” that means: this is a defective protein.” Because, in fact, the protein in question does add specific information; the information necessary to activate the heat shock response, and it does so by adding a random sequence made up of two amino acids. Is the fact that this random sequence has a functional effect, what you don’t like?AVS
January 8, 2015
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