Tiny ion is crucial for HIV replication, say chemists(medicalxpress.com)
medicalxpress.com
Tiny ion is crucial for HIV replication, say chemists
https://medicalxpress.com/news/2023-01-tiny-ion-crucial-hiv-replication.html
24 comments
Is there such a thing as a non-tiny ion? I suppose a very long carbon chain might count. It's strange that the article doesn't even name it: inositol hexakisphosphate, a.k.a phytic acid https://en.wikipedia.org/wiki/Phytic_acid.
Albeit as a non-chemist, I'm surprised ions get as big as phytic acid.
I'm not a chemist.
But by common definitions aren't all acids (an)ions?
(As in bronstead Lowry acids).
So why is it being called an ion and not just acid?
But by common definitions aren't all acids (an)ions?
(As in bronstead Lowry acids).
So why is it being called an ion and not just acid?
I am also not a chemist.
A (bronstead) acid is a proton donor. An atom that donates a proton becomes an (an)ion. The acid is not the anion; the anion is the conjugate base of the acid.
Not all acids form an anion; hydronium is an ion that becomes neutral when it donates a proton.
I do not know why the article used the term ion here. I am guessing it is because the abstract refers to IP6 as a polyanion. It is not referred to as an acid, because it is not participating in acid/base chemistry (though I tried reading the paper and the mechanism is well over my head).
A (bronstead) acid is a proton donor. An atom that donates a proton becomes an (an)ion. The acid is not the anion; the anion is the conjugate base of the acid.
Not all acids form an anion; hydronium is an ion that becomes neutral when it donates a proton.
I do not know why the article used the term ion here. I am guessing it is because the abstract refers to IP6 as a polyanion. It is not referred to as an acid, because it is not participating in acid/base chemistry (though I tried reading the paper and the mechanism is well over my head).
> An atom that donates a proton
An atom can donate an electron (and become a cation), but how can an atom donate a proton? By nuclear fission?
edit: but, a molecule can donate a proton (an H+), and the molecule itself will become an anion
An atom can donate an electron (and become a cation), but how can an atom donate a proton? By nuclear fission?
edit: but, a molecule can donate a proton (an H+), and the molecule itself will become an anion
Good point, I meant to say molecule, not atom. I blame lack of coffee.
I think because they're talking about individual molecules fitting into the solid structure, not lots of molecules in solution.
I think the general idea is that the biggest ion 2 angstrom tops, more likely 0.2 angstrom, whereas most proteins (where the ion is used) are 30-50 angstroms across (and note this is 3d, a 1 angstrom ion is 1000 times smaller than a 10 angstrom protein). And the whole HIV virus particle is ~1200 angstrom across.
So that ion is like a mouse compared to a skyscraper.
So that ion is like a mouse compared to a skyscraper.
I didn't know people used the term "ion" like this, either.
Not sure how could this lead to any treatment. I don't think we can just knock out production of IP6. It's produced in the body so it probably has some role there.
We'd have to target hiv infected cells specifically and if we could do that then why not just kill them.
We'd have to target hiv infected cells specifically and if we could do that then why not just kill them.
FTA
> The result may explain the promise of a drug currently in human trials: lenacapavir. Lenacapavir "competes" with IP6, stabilizing the six-sided structures over the five-sided ones. This tilts the process to favor open-ended tube shapes instead of enclosed capsids.
> The result may explain the promise of a drug currently in human trials: lenacapavir. Lenacapavir "competes" with IP6, stabilizing the six-sided structures over the five-sided ones. This tilts the process to favor open-ended tube shapes instead of enclosed capsids.
Just a small note - lenacapavir has been approved by the FDA since December 2022
Can someone explain how these proteins get to form the capsid structure? Do they just float around in the cytoplasm and self-assemble through molecular forces? Or there are other specialized machines that do the assembling? How are the machines produced in the first place? It seems so improbable, like throwing a bunch of bricks near each other and getting a house
The process that converts the chain of amino acids into a finished protein is called "protein folding", and yes, other proteins are involved, but the protein also influences its own folding to some degree: some parts want to be together, others want to be apart, etc. Those aid proteins, called chaperones, too, are created by the same process they are part of. Viruses use the assembly proteins of the host cell, but sometimes they bring their own proteins that are involved in some parts of the process (but not all of it).
For the cell, there is an obvious chicken/egg problem here: if it needs such a process to turn RNA into chaperone proteins, and in order to clone RNA you need proteins, too, then what came first, the protein or the RNA? The process of how life evolved in this early stage is very poorly understood, but it is believed that everything evolved from RNA (RNA world hypothesis).
https://en.wikipedia.org/wiki/Protein_folding
For the cell, there is an obvious chicken/egg problem here: if it needs such a process to turn RNA into chaperone proteins, and in order to clone RNA you need proteins, too, then what came first, the protein or the RNA? The process of how life evolved in this early stage is very poorly understood, but it is believed that everything evolved from RNA (RNA world hypothesis).
https://en.wikipedia.org/wiki/Protein_folding
I won't pretend to be able to give an accurate answer but if you wonder about this kind of things, this book is a masterpiece [1]. Yes, it's expensive and big, but also fascinating and very well prepared.
https://www.amazon.com/Molecular-Biology-Sixth-Bruce-Alberts...
https://www.amazon.com/Molecular-Biology-Sixth-Bruce-Alberts...
great recommendation. from that book
"We can take a piece of DNA from a human cell and insert it into a bacterium or a piece of bacterial DNA and insert it into a human cell, and, with only a few minor modifications, the information will be successfully read, interpreted, and copied"
that is truly amazing...
"We can take a piece of DNA from a human cell and insert it into a bacterium or a piece of bacterial DNA and insert it into a human cell, and, with only a few minor modifications, the information will be successfully read, interpreted, and copied"
that is truly amazing...
You've got the idea! I'm not an HIV biologist, but typically these viruses utilize poly-cistronic transcripts. What that means is the proteins are made off the same mRNA so when they come off the ribosome they are local to the previous and next proteins being decoded. It's a very recurring theme in biology to have high _local_ concentration of things that you'd like to do a thing together.
Imagine a box of magnitiles that you just start throwing around the room. Well, instead of throwing them around the room and hoping they stick to each other, what if you only threw them around inside another box, which you were shaking vigorously? Well, you'd expect the magnitiles to find each other and stick to each other. Now imagine you attach each magnitile by a 1cm string and then throw them into a box and right after you through a string of 100 magnitiles, you start a new string of 100 magnitiles and throw that into the box instead of throwing it at the other side of the room.
The idea being concentration depends on the denominator of the volume you're in. If you have 2 things in a 1x1 meter box, you have a much higher concentration and therefore it is much more likely two things will bump into each other a lot than if you have 2 thing in a 1000 x 1000 meter box.
Also, a lot of these systems get made on the endoplasmic reticulum and so it then becomes a 2D search problem instead of a 3D search problem, reduces the volume of your box by an entire dimension! AND viruses tend to make little cordon off spots inside the cell where all their bits congregate, further increasing the chances they bump into each other the right way because, again, the _local_ concentration is super, super high.
Also keep in mind things at this scale bump into each other a mind boggling number of times per unit time. Like an asstillion number of times every second. Eventually they hit each other in the right way to stick together like magnitiles. They also vibrate constantly, which is called "exploring the conformational space". Anyway, I think you see my points.
Imagine a box of magnitiles that you just start throwing around the room. Well, instead of throwing them around the room and hoping they stick to each other, what if you only threw them around inside another box, which you were shaking vigorously? Well, you'd expect the magnitiles to find each other and stick to each other. Now imagine you attach each magnitile by a 1cm string and then throw them into a box and right after you through a string of 100 magnitiles, you start a new string of 100 magnitiles and throw that into the box instead of throwing it at the other side of the room.
The idea being concentration depends on the denominator of the volume you're in. If you have 2 things in a 1x1 meter box, you have a much higher concentration and therefore it is much more likely two things will bump into each other a lot than if you have 2 thing in a 1000 x 1000 meter box.
Also, a lot of these systems get made on the endoplasmic reticulum and so it then becomes a 2D search problem instead of a 3D search problem, reduces the volume of your box by an entire dimension! AND viruses tend to make little cordon off spots inside the cell where all their bits congregate, further increasing the chances they bump into each other the right way because, again, the _local_ concentration is super, super high.
Also keep in mind things at this scale bump into each other a mind boggling number of times per unit time. Like an asstillion number of times every second. Eventually they hit each other in the right way to stick together like magnitiles. They also vibrate constantly, which is called "exploring the conformational space". Anyway, I think you see my points.
Thank you for this, it really helped me visualise the process!
I find it amazing how the proteins not only have to create the shape in the end, but they also need to be able to snap together in the right conformation and avoid snaping together with other molecules that happen to be around there. And they must evolve that function in the first place. I intuitively have a hard time grasping what simple processes repeated an inumerable amount of time can produce in the end. And yet here we are.
I find it amazing how the proteins not only have to create the shape in the end, but they also need to be able to snap together in the right conformation and avoid snaping together with other molecules that happen to be around there. And they must evolve that function in the first place. I intuitively have a hard time grasping what simple processes repeated an inumerable amount of time can produce in the end. And yet here we are.
Yea, humans are unable to mentally understand deep time or small scales. We think way too linearly. Glad it made sense!
watch the 3D animation video here. it's pretty amazing and this knowledge is the result of decades of research condensed into a single animation. https://blogs.scientificamerican.com/observations/watch-the-...
The capsid is one thing but it's utterly mind boggling to me that you make a stretch of amino acids and they reliably crumple into like an enzyme.
That and prions are crumpled proteins that crumble other similar proteins into themselves. Mental!
That and prions are crumpled proteins that crumble other similar proteins into themselves. Mental!
My first question would be: What if you increase the concentration of IP6? The idea being to promote the creation of many 5-sided things, increasing curvature all over and creating capsids too small to enclose the genetic material.
If nothing else, the standard downside would apply: IP6 is not a novel molecule and would probably not be patentable.
If nothing else, the standard downside would apply: IP6 is not a novel molecule and would probably not be patentable.