Do amino-acids spontaneously bond within a cell?

[icakeov]

I was wondering whether it is possible for amino acids that end up in a cell (ready to be made into proteins) to spontaneously start to bond in the cytoplasm (or wherever the routing channel is I guess) and create randomly floating short strands of polymers?

Furthermore, can it ever happen that once in a DNA structure for example, that amino acids from one strand could attract another strand and then break off and bond? My guess is that this is a straight no, but I have heard about the "dropped genes" or something to that end.

 

[jim mcnamara]

#2 must have a typo or something. Amino acids are not necessarily attracted to DNA strands or vice versa. Can you clarify a bit?

#1. On a common basis, no. peptide bonds require energy.

And yes, amino acids may undergo unintentional (from a human's point of view anyway) reactions when "floating" around. Commonly in mammals, proteins and single amino acid molecules can undergo glycosylation. The amino acids react with glucose.

Example: Higher levels of blood glucose in diabetics increases this reaction, the more common one is for glucose to damage proteins in cells. Like retinal cells (retinopathy) or nerve cells (neuropathy). Uncontrolled diabetes is a very common cause of blindness.
From NIH: https://medlineplus.gov/magazine/issues/summer08/articles/summer08pg14-15.html

The process is called glycosylation:
https://en.wikipedia.org/wiki/Glycosylation.

It is, AFAIK, extremely less common for amino acid > amino acid reactions to occur as you describe.. Because it requires energy. See:
https://en.wikipedia.org/wiki/Peptide_bond

Amino acids under reasonable storage have shelf stability. If lots of spontaneous reactions occurred then you would see dipeptides and poly-peptides forming.
Aspartic acid added to tortillas with moisture in them: http://www.traditionaloven.com/food...lour-shelf-stable/aspartic-acid-d-aa-asp.html
And, no, I have no clue why you would want aspartic acid added to tortillas. Supplement companies run amok? Anybody?

There are lots of other kinds of reactions on free amino acids, like formation of amides:
This paper talks about a reaction with free aspartic acid -> http://onlinelibrary.wiley.com/doi/10.1111/j.1399-3011.1987.tb03390.x/abstract

 

[icakeov]

That is super helpful @jim mcnamara , thanks!

Yes, the DNA and amino acid reference was a total mistake, although, I was going to go in the same direction with this question with nucleotides too...

So, the amino acids can react, but not in the direction of creating proteins, but different molecules that are not necessarily useful and even damaging.

Basically, without ATP swimming around to help create the peptide bond, these amino acids wouldn't create long polypeptide bonds. This would mean that pre mitochondria "invention", early life would have had to bank on random ATP molecules swimming around to create the loop of life? Or would it have been some other "contributor" back in those days?

Thanks again!

 

[Ygggdrasil]

When thinking about the origin of life, it's important to remember that proteins likely evolved relatively late in the game. It is thought that pre-biotic life consisted of an RNA world where RNA served both as a genetic material as well as the catalyst for carrying out chemical reactions. Thus, when considering the origin of life, one needs to think of way that long, functional RNA molecules could form spontaneously without the help of other enzymes.

A recent paper from Jack Szostak's group at Harvard tacked this challenge. Here's a summary of the paper:

Though defining what makes something “alive” has proved challenging, one crucial feature of living things is the ability to copy genetic information and pass it on to the next generation. Nowadays, enzymes called polymerases copy genetic information encoded within the DNA of living cells. However, when life on Earth began approximately four billion years ago, polymerases had not evolved yet. This means that the genetic information of the first cells had to be copied some other way.

The earliest life on Earth is unlikely to have used DNA to store its genetic information, and probably used a closely related molecule called RNA instead. Like DNA, RNA is made up of four smaller building blocks joined together to form long chains. The building blocks of RNA are commonly referred to using single letters: A, C, G and U. Previous studies have shown that it is possible to copy RNA without enzymes, but for only two of the four RNA letters, namely C and G.

Prywes et al. wanted to know if it was possible to create a chemical system, without polymerases, in which all four RNA letters could be copied. The experiments showed that strings of RNA that were three letters long could catalyze RNA copying, just as long as they were chemically activated. That is to say, these short RNA strings allowed RNA to be copied without enzymes if they had a chemical group at one end that made them more reactive.Each short catalyst helped copy one of the four RNA letters, and adding several into one reaction meant that longer sequences containing all four RNA letters could be copied.

Prywes et al. then used these short catalysts to copy an RNA molecule that itself acts a bit like an enzyme, and confirmed that a significant portion of this molecule could be copied without any polymerases. Further work is now needed to see if it is possible to copy other RNA sequences, and especially longer ones, without enzymes. Another challenge for the future would be to attempt to copy an RNA sequence multiple times without enzymes; a challenge that the earliest ancestors of cells on Earth must have overcome to pass their genetic information down through the generations.

Prywes et al. 2016 Nonenzymatic copying of RNA templates containing all four letters is catalyzed by activated oligonucleotides. eLife 5: e17756.

The paper is freely accessible here: https://elifesciences.org/content/5/e17756

 

[icakeov]

Many thanks @Ygggdrasil! Seems like science is getting ever closer to this one.

 

[icakeov]

Speaking of the early ancestors, I understand that the "last universal common ancestor" (LUCA) had a molecular set-up that every living being today has. I am curios if the same could be said about the interactome LUCA produced?

Are there actually certain interactomes that are still today shared amongst every single living being? My guess is that it is a clear yes, but then again, maybe there has been some mutations that changed things.

And speaking of interactomes, I am guessing that interactome doesn't have to exclusively include the molecules produced by the organism itself, or does it? What I mean by this, if 10 proteins interact in a chain, and one of them was some ligand from the outside, would this be considered an interactome that "belongs" to this organism?

Many thanks again!

 

[Ygggdrasil]

Speaking of the early ancestors, I understand that the "last universal common ancestor" (LUCA) had a molecular set-up that every living being today has. I am curios if the same could be said about the interactome LUCA produced?

Are there actually certain interactomes that are still today shared amongst every single living being? My guess is that it is a clear yes, but then again, maybe there has been some mutations that changed things.

What do you mean by interactome? If by interactome, you mean a set of proteins form conserved macromolecular complexes, then they certainly do exist. For example, the ribosome comes to mind as a well conserved complex of many protein and RNA molecules whose interaction is conserved across all known forms of life. I'm not sure whether there has been any comprehensive look at this question, though similar studies have defined, for example, the panorama of macromolecular complexes present in the ancestor to all animals (http://www.nature.com/nature/journal/v525/n7569/full/nature14877.html).

 

[icakeov]

Wiki defined interactome as the "whole set of molecular interactions in a particular cell" and The proteome is the entire set of proteins expressed by a genome of any given organism, so I thought the reference is toward interactions rather than the molecules themselves. That's why I thought if the molecules started interacting with other molecules that would change the "interactome"? And also that is why I was asking whether an "interactome" includes interactions with molecules from the "outside"..

Also, when we say "protein complex", does that mean bunch of different proteins that can create a chain reaction or is it more in the line of "#4 folding" where they all group into one big molecule do that does a specific function?

Thanks so much again for clarifying all this.

(I just got the app too! Sweet!)

 

[Fervent Freyja]

I'm curious @icakeov, are you majoring in biology? If not, you should! Or are you still in high school?

 

[icakeov]

Oh, I wish. In the last two years I got incredibly interested in this subject, but I don't have the time and resources to pursue it academically, for now, this will remain an endeavor that doesn't involve a diploma. Ironically, when I was in high-school, I really disliked biology and chemistry. Go figure. Thanks Fervernt Freyja.

 

[Ygggdrasil]

Wiki defined interactome as the "whole set of molecular interactions in a particular cell" and The proteome is the entire set of proteins expressed by a genome of any given organism, so I thought the reference is toward interactions rather than the molecules themselves. That's why I thought if the molecules started interacting with other molecules that would change the "interactome"?

Ok, I just wanted to be sure about your question. You are using the term correctly. The interactome is the whole set of molecular interactions within a particular cell, and some of those individual molecular interactions are likely conserved across all known forms of life.

And also that is why I was asking whether an "interactome" includes interactions with molecules from the "outside"

Interactomes typically refer to the set of protein-protein interactions, but yes, interactions with exogenous components that are not produced by the cell probably should also be included. Metabolism would be interesting to examine. There are probably some metabolic pathways that have been conserved to take molecules from the environment and convert them into the building blocks of life.

Also, when we say "protein complex", does that mean bunch of different proteins that can create a chain reaction or is it more in the line of "#4 folding" where they all group into one big molecule do that does a specific function?

A protein complex refers to the later case, where various proteins come together to form one larger assembly that performs a specific function. A set of proteins that act in series, for example, to convey a signal from a transmembrane receptor to the nucleus is more often referred to as signal transduction pathways or cascades.

 

[BillTre]

Interactomes typically refer to the set of protein-protein interactions, but yes, interactions with exogenous components that are not produced by the cell probably should also be included. Metabolism would be interesting to examine. There are probably some metabolic pathways that have been conserved to take molecules from the environment and convert them into the building blocks of life.

These relationships would be interesting in host-symbiont (or parasite) relationships.
One might expect these to involve interspecies cell-cell recognition and metabolic interactions between species.

 

[icakeov]

Great! Thanks so much @Ygggdrasil, that is really helpful!
And yes, the interactions of symbiotic bacteria is a great example @BillTre

I do have two more things/concepts that are still a bit unclear:

...and some of those individual molecular interactions are likely conserved across all known forms of life.
... A set of proteins that act in series, for example, to convey a signal from a transmembrane receptor to the nucleus is more often referred to as a signal transduction pathways or cascades.

Besides individual molecular interactions being conserved across all known forms of life, would it be correct to say that there are certain signal transduction pathways that are also conserved across all life?

A protein complex refers to the later case, where various proteins come together to form one larger assembly that performs a specific function.

For example, the ribosome comes to mind as a well conserved complex of many protein and RNA molecules whose interaction is conserved across all known forms of life.

(From the other parallel thread:)

The large multi-protein complex that carries out DNA replication is often referred to as the replisome.

I think the above referenced few paragraphs is where I got confused.
When you referred to the "conserved complex", looks like you were talking about many protein and RNA molecule interactions inside the ribosome, not the interaction of the ribosome with many protein and RNA molecules, so the ribosome would be referred to as the "protein complex"? On the other hand, replisome (also referred to as a "protein complex"), seems to refer to all the different, "independent" proteins that are in charge of replicating DNA?

 

[Ygggdrasil]

Besides individual molecular interactions being conserved across all known forms of life, would it be correct to say that there are certain signal transduction pathways that are also conserved across all life?

That I am less sure about. For example, in animals, phosphorylation of serine, threonine or tyrosine residues is a very common mechanism in signal transduction pathways. Bacteria also have some signaling pathways involving phosphorylation but the phosphorylation occurs on histidine residues instead.

When you referred to the "conserved complex", looks like you were talking about many protein and RNA molecule interactions inside the ribosome, not the interaction of the ribosome with many protein and RNA molecules, so the ribosome would be referred to as the "protein complex"? On the other hand, replisome (also referred to as a "protein complex"), seems to refer to all the different, "independent" proteins that are in charge of replicating DNA?

There are many different kinds of protein complexes in cells. On the one hand, there are very stable protein complexes that are typically tightly assembled and perform one integrated function, like the ribosome. There are other complexes, however, that form only transiently. Sometimes the components are scattered throughout the cell, and only at certain points when the complex is needed to the components assemble together to form the complex (the replisome is a good example as is the spliceosome). Protein complexes can even change composition as they perform their function (RNA polymerase II is a good example. At the beginning of transcription it helps recruit enzymes involved in mRNA capping, later it recruits with splicing factors, and as it approaches the end of the gene, it recruits the proteins involved in cleaving and polyadenylating the mRNA transcript).

 

[icakeov]

Understood! Wow, what incredible complexity of the machinery of life. Thanks again for all this!