PROTEIN FOLDING
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- čas přidán 1. 03. 2019
- Proteins are made up of folded polypeptide chains, which are composed of 20 different amino acids, each with different chemical properties, that are linked to each other via covalent peptide bonds. The sequence of atoms repeating to form the peptide bonds is called the polypeptide backbone. The side chain of each amino acid, which is the part that makes it different from the other 19 amino acids, can be either polar or nonpolar. The polypeptide chain can fold in many different ways, called “conformations”. Conformations are the spatial arrangement of atoms that can result from movement of atoms without breaking of bonds.
Protein structure can be described in terms of four levels of organization - primary, secondary, tertiary, and quaternary structure. The primary structure is simply the amino acid sequence of the polypeptide chain, and it is important to remember that this sequence contains all the information necessary for the higher orders of structure. The secondary structure is formed by hydrogen-bond interactions of adjacent amino acids. Large numbers of such local interactions form α-helices and β-pleated sheets. The tertiary structure is a more compact, 3-dimensional shape. Large proteins often consist of several protein domains, which are distinct structural units that fold somewhat independently from one another. Quaternary structure is found in those proteins that have 2 or more interacting polypeptide chains, which are then termed subunits.
Let’s examine these four levels of organization in more detail. The primary structure is determined by covalent bonds holding amino acids in a specific order. However, higher orders of structure are primarily dictated by non-covalent forces - ionic bonds, hydrogen bonds, van de Waals, and hydrophobic interactions. The combined strength of large numbers of noncovalent bonds in a protein’s folding pattern determines the stability of any given conformation. The final conformation of a protein is specified by its amino acid sequence and is typically the one that minimizes its free energy.
Secondary structures include α-helices and β-sheets. An α-helix occurs where a polypeptide chain coils like a spring, with one turn every 3.6 amino acids. In α-helices, the N-H of a peptide bond is hydrogen bonded to the C=O of another peptide bond which is one coil up in the helix structure. Note also that all the N-H groups point in one direction - towards the N-terminus - and all the C=O groups point in the opposite direction - towards the C-terminus - and this is what gives the polypeptide chain polarity. The C-terminus is partially positively-charged, while the N-terminus is partially negatively-charged.
β-sheets can form parallel chains, which are made from neighbouring chains running in the same direction, or antiparallel chains, which are made from a polypeptide chain that folds back and forth on itself so that nearby sections run in opposite directions. While hydrogen bonds in an α-helix are intrastrand, hydrogen bonds in β-sheets are interstrand.
Tertiary structure formation can be nucleated by the pattern of polar and nonpolar amino acids in a polypeptide chain, which plays a central role in determining the protein’s final conformation . This is because hydrophobic molecules, such as the nonpolar side chains of certain amino acids, are entropically driven together in an aqueous environment. This limits their disruption of the hydrogen bonding of surrounding water molecules. As a result, nonpolar amino acids tend to be found predominantly in the interior of proteins. Meanwhile, polar amino acids face the outside of the protein, forming hydrogen bonds with one another and the water molecules around the protein. Those polar amino acids that are on the inside of the protein bond with one another or with the polypeptide backbone.
It is thought that protein folding happens roughly along the following lines. Secondary structures form first. Hydrophobic collapse, during which non-polar amino acids aggregate, happens next. Long-range interactions between secondary structures cause further folding to occur. Throughout this process, there may be one or more intermediate states, such as what has been termed a “molten globule”.
As a final note, there are three basic classes of proteins, which are distinguished based on shape and solubility - globular, fibrous, and membrane proteins. Globular proteins are spherical in shape, with as little surface area per volume as possible. These proteins are marginally stable, and this marginal stability facilitates motion, which in turn enables function. Hydrophilic amino acids occupy this small surface area, making these proteins highly soluble in water. Fibrous amino acids are simple, linear structures which have structural roles and are insoluble. Lastly, membrane proteins are associated with cell membranes.
Cell Membrane model from www.turbosquid.com/3d-models/...
only video that explained protein folding well!! thank you so much!!
@ Neural Academy, there is a mistake at 2:06. The Carboxyl end is the partially negative end and the amino end is partially positive.
correct, I did not notice that.
Thank you very much, you probably get loads of gratefulness, but you helped me a lot as well.
Thank you, this is helpful for a investment in protien engineering. Once AI takes over it is my hope that its used for good not evil.
excellent concise explanation
this was everything I needed! love your presentation style, would love to see one on glycolysis!
You all prolly dont give a shit but does anybody know a method to log back into an Instagram account?
I was dumb forgot my password. I would appreciate any tricks you can offer me!
@Alfredo Major instablaster :)
Nice communication skills.
I am also intrigued by certain issues.
1. Must every amino acid present in a protein participate in bonding during the Protein folding process?
2. What is the process of breaking up protein to small clusters to aid computation?
Thanks for the help!
A helpful breakdown of protein structures, thank you! A video on enzymes (types, kinetics, cofactors, etc) would fit in with the protein and hemoglobin videos. You'd get my view/upvote!
I'm so glad you found my video helpful!! ^_^ I've jotted down the topic and will make a video on it very soon :-)
1 week to put it together! Way to go, thank you again for helping improve understanding of these complicated topics!@@NeuralAcademy
@@hughgeary7356 No problem :-) I'll be putting up part two, which will be discussing everything else, in about 3-4 weeks I expect.
@Neural Academy Is protein solubility directly proportional to protein folding ?
there is a mistake at 2:06. The Carboxyl end is the partially negative end and the amino end is partially positive.
27
Very very useful
Interesting!
Thank you so much!
the amino terminus has a positive polirary and the carboxyl terminus has negative polarity
Yes, this was confusing me in the video.
So the end polarity is basically flipped?
why is this so?
i am confused too
Good info. Ty
Can you please make a video showing how prions interfere with protein folding?
you're amazing
I need a topic about from gene to hero. Since it's going to hard to understand neural cells functions att all by just experiment. They have to be virtually simulated!
I have no idea what I just watched.
I came to watch this because I read a book on chemical physics
Współczuje otoczeniu
This requires at least college level gen chem to really understand fully.
@@musashimiyamoto9035I’m still 15 years old and study these things💀
I tried figuring out what "Folding at Home" is making my computer do. I still don't understand but I sure hope it helps!
pain.
Wow did my brain get a whole lot of information overload. I was looking to learn how to fold panties. I accidentally messed up my step sisters undies drawer. I can't get em to look like the other ones in the drawer. You know what?.tmi. sry
I understood only a little
who is here after learning about alphafold 2?
Me
Your framework of 4 levels of organization is confusing. There are signals that suggest the 4 levels are progressive stages every protein goes through --- that all proteins progress through all 4 stages.
Yet there are other indications that you're saying they are distinct categories of organization, and any given protein falls into one of the 4.
One factor that creates this confusion is that you include the first level as one of the 4. So, if your point is that these are 4 distinct categories of organization, and any given protein falls into one of the 4, then you're confusing the issue by including the first category --- the chain. Because, as I understand it, ALL proteins begin as a chain that is then folded. So the first category --- the chain --- should not be included as a category of organization. You should instead say that all proteins begin as a polypeptide chain, and then fall into one of these 3 categories.
Also, the fact that you call them "levels of organization" is confusing. Saying they are levels of organization, and including the polypeptide chain as the first level, suggests that all proteins progress through the 4 levels. This is because, again, all proteins begin as a polypeptide chain, and then fold. So if the polypeptide chain is the first category, and ALL proteins begin at that stage, then it's suggesting that they all then continue through the next 3 stages, ending at stage 4.
Can you explain what you mean?
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there are more than 20 amino-acids, just saying 🤷♂️🤷♂️
people need wake up. God is real
Its just the perfect idea. To say it is "real" is about as useful as saying "existence exists"