Protein Folding Mechanism

Protein folding is the physical process by which a protein chain acquires its native 3-dimensional structure, a conformation that is usually biologically functional, in an expeditious and reproducible manner. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil. Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA to a linear chain of amino acids. This polypeptide lacks any stable (long-lasting) three-dimensional structure (the left hand side of the first figure). As the polypeptide chain is being synthesized by the ribosome, the linear chain begins to fold into its three dimensional structure. Folding begins to occur even during translation of the polypeptide chain. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein (the right hand side of the figure), known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence or primary structure (Anfinsen's dogma).[2] The energy landscape describes the folding pathways in which the unfolded protein is able to assume its native state. Experiments beginning in the 1980s indicate the codon for an amino acid can also influence protein structure.
The correct three-dimensional structure is essential to function, although some parts of functional proteins may remain unfolded, so that protein dynamics is important. Failure to fold into native structure generally produces inactive proteins, but in some instances misfolded proteins have modified or toxic functionality. Several neurodegenerative and other diseases are believed to result from the accumulation of amyloid fibrils formed by misfolded proteins. Many allergies are caused by incorrect folding of some proteins, because the immune system does not produce antibodies for certain protein structures.
Primary Structure :
The primary structure of a protein, its linear amino-acid sequence, determines its native conformation.[7] The specific amino acid residues and their position in the polypeptide chain are the determining factors for which portions of the protein fold closely together and form its three dimensional conformation. The amino acid composition is not as important as the sequence.[8] The essential fact of folding, however, remains that the amino acid sequence of each protein contains the information that specifies both the native structure and the pathway to attain that state. This is not to say that nearly identical amino acid sequences always fold similarly.[9] Conformations differ based on environmental factors as well; similar proteins fold differently based on where they are found.
Secondary Structure:
Formation of a secondary structure is the first step in the folding process that a protein takes to assume its native structure. Characteristic of secondary structure are the structures known as alpha helices and beta sheets that fold rapidly because they are stabilized by intramolecular hydrogen bonds, as was first characterized by Linus Pauling. Formation of intramolecular hydrogen bonds provides another important contribution to protein stability. Alpha helices are formed by hydrogen bonding of the backbone to form a spiral shape (refer to figure on the right).The beta pleated sheet is a structure that forms with the backbone bending over itself to form the hydrogen bonds (as displayed in the figure to the left). The hydrogen bonds are between the amide hydrogen and carbonyl carbon of the peptide bonds.
Tertiary Structure
The alpha helices and beta pleated sheets can be amphipathic in nature, or contain a hydrophilic portion and a hydrophobic portion. This property of secondary structures aids in the tertiary structure of a protein in which the folding occurs so that the hydrophilic sides are facing the aqueous environment surrounding the protein and the hydrophobic sides are facing the hydrophobic core of the protein.[11] Secondary structure hierarchically gives way to tertiary structure formation. Once the protein's tertiary structure is formed and stabilized by the hydrophobic interactions, there may also be covalent bonding in the form of disulfide bridges formed between two cysteine residues. Tertiary structure of a protein involves a single polypeptide chain; however, additional interactions of folded polypeptide chains give rise to quaternary structure formation.
Chaperone Concept : The Chaperones assist in the correct folding pattern of a protein.If Chaperone fails to do so then Protein ultimately becomes Prion protein which gives rise to several diseases lile Kuru , Scrapie disease and Alziemers.

[@Shannu_1903]

I just love the fact that u did everything precisely and did not miss the important stuff...but yet saving time....thank you so much!

[@hussainbiology]

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Excellent presentation..to the point no deviation..its fast nd accurate...it saves me a lot of time during my pg preparation for biochemistry..thank u

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Great analysis

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Thank you!! Finally I understand it.

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[@filmedbyanam]

Great Video. Very detailed with what was most important from these processes!

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[@TheeBotany]

Excellent. Thank you

[@thenaturalsourceofourhealth]

Great vid! Presentations don't get much clearer than this!

[@hussainbiology]

thanks for appreciation Sir

[@aamir122a]

Well presented, understood the protein folding ( at least at a basic level ) in one go.

[@hussainbiology]

Thanks for appreciation

[@wafaawardah3264]

Oh wow. Amazing video. Thank you very much.

[@hussainbiology]

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[@apurvakmr]

Beta sheets have several beta strands with inter strand H bond. At minimum level, beta strands are a secondary structure

[@meenaramalingam8874]

I took notes from your explanation and diagram only !! Thank you !

[@hussainbiology]

Thanks Meena for appreciation..... Really Glad to know that it helps,.,...

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[@hussainbiology]

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thank you so so so much! a real life saver!

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[@prashantj50]

Thanks

[@Alchemist_171]

Are hydrophobic effects necessary for stability of a protein or is it just H-bonding? Particularly asking because I came across such question and I answered H-bond. Wondering if I was right.

[@avicennawater]

How do amino acids or cell in the process of forming fold to get to the ultimate final shape that cell needed to perform certain function ? I am alluding to the protein folding problem

[@georgejoseph1430]

awesome job man! keep it up!

[@hussainbiology]

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[@galapagosworm3813]

Concise and Precise. Well Done.

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Thank you,sir🙏

[@shirse9331]

Ohh sir...thank you...sir I have a request..can you please make the lecture video on the topic of ""Thermodynamics of protein folding""

[@luljetegecaj8195]

Nicely explained..thanks so much!! :)

[@hussainbiology]

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[@KenJackson_US]

Are chaperone proteins universal? That is, do they help any protein fold correctly? Or is there one unique chaperone per problematic protein?

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I liked this video , thanks 👍

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beautiful accent, very soothing to hear

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[@KomalKumari-jw6lz]

Which bonding involves in target proteins interacting with chaperones?

[@riyasharma6050]

Thank you so much

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[@beinghuman4457]

What will happen if hydrophobic region is kept on outer surface instead of hydrophilic part of protein?

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[@hussainbiology]

Thanks dear,,,,, glad to know that you love the accent......

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Thanku so much 🤗🤗

[@dr.doha_harby]

Wow👌👌

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[@hananerose8669]

Hi can I ask you what mines a floded three dimensional region of a protein that forms the basic unit of tertiary structure

[@samanthajoanamariemallari968]

Whoah! Thank you🥺 this is very informative ❤️

[@hussainbiology]

thanks for appreciation

[@rahinadalvi8787]

Do fibrous protein exist in quaternary structure conformation or only globular proteins. And if yes den how polar and non polar separation occurs?

[@apurvakmr]

They do. Best example us the triple helical arrangement of collagen

[@kaipabingwit3276]

THANKS MATE!

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U are welcome Buddy...Keep supporting

[@aakifahaslam4623]

So well explained

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Nice.

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Thank you🥺💖

[@hussainbiology]

You’re welcome 😊

[@ramelakoumrouyan4664]

Nice lecture! Are there any exceptions in the boy where 2ndary structure proteins are functional? (2ndary is when the bonds like disulfide and others form no?)

[@hussainbiology]

Hi Ramela , first of all thanks for appreciation........Now talking about proteins,,,,, I think Apolipoprotein E found to play crucial role in Alzheimer's disease has got functional secondary structure in the form of linear Alpha helices. ( still i am not 100% sure ). Thanks again

[@hussainbiology]

Also watch this video also kzbin.info/www/bejne/Zoepd2pjfN6LZpI

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Seriously Sir👍its just awsum way of explaining da things...takes no tym to feed in mind. Beautifully way of presenting through diagram by making it colourfull & neat. Eye catching👌handwriting n diagram. Am going to suggest frndz to for dis channel. Thank you🙏

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Excellent presentation...its help me a lot 🙏🙏🙏🎉.

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Glad to hear that

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Very very very informative

[@excitegamer5084]

hope so my lecture of tomorrow will be good❤️🥹

[@chaus0808]

Nice video.....keep it up!!!

[@hussainbiology]

Thanks bro.....Keep supporting

[@christianjoshuabanayat202]

why does the protein dont fold sometimes?

[@asnanaval]

Is there any videos of molten globule state of protein

[@hussainbiology]

Not yet... Asna

[@rimshakhan2672]

Wonderful work sir. It helped me in my presentation

[@hussainbiology]

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[@rakshitatambe8627]

Thank you sir very nicely explained 🤗

[@hussainbiology]

thanks for appreciation

[@alyssum1426]

What is parsley?

[@varunnaidu9410]

Example for primary secondary tertiary and quaternary protein should have Been told

Thank Mr. Hussain

[@hussainbiology]

my pleasure

[@farispawan8756]

Excellent

[@hussainbiology]

thanks for appreciation

[@muhdhasni3682]

I think for B sheets, the hydrogen bonding is presence in interchain right ?

[@hussainbiology]

There will always be intra interactions..... Like intramolecular hydrogen bonds between beta sheets..... If you say interchain , that means two different molecule ( chains) form hydrogen bonds but in Beta sheets we always have same molecule and we will always form intramolecular hydrogen bonds.

[@georgelacey4816]

Very complicated process explained simply.

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[@srividyaamirishetty5724]

Super to easily understood

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All video Just awesome for quick understanding ❤❤😊

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Vry helpful......thnx a lot sir

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you are welcome...

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Thank you for ds video.. Its good n easy to undrstand.. N also easy to prepare

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@@hussainbiology thank you sir

[@michaeleisenberg7867]

Dear Dr. Hussain, Another superb video! Thank you. Have scientists tried to predict how a polypeptide will fold? Does the technology exist for a scientist to build de novo a functioning protein or enzyme?

[@hussainbiology]

Thanks for appreciation...Yes the technology exits

[@avicennawater]

The real question is really how does the polypeptides know it’s path to final shape in less than milliseconds let alone knowing what does the cell need to make such protein

[@michaeleisenberg7867]

@@avicennawater My guess is if you connected the same peptides in the same order they would fold the same way every time. It is because of the acid and base charges at each end of the individual amino acids, and the R groups. I think quantum mechanics and thermodynamics attempts to explain the mechanism of atomic interactions such as folding. It happens super fast. If you believe in evolution those proteins would not be here, nor you or I, if they did not fold into a functioning protein. Polypeptides evolved thru trial and error. The ones that folded into useful proteins were selected to stay. The duds were not promoted. Also chaperone proteins evolved (the same way) to help some proteins fold correctly. Not all proteins need the help of chaperones. Usually, if a protein folds incorrectly it is ubiquitinated and sent to the garbage heap (the proteasomes).

[@ramchandrasuthar2848]

Very nice SIR

[@hussainbiology]

thanks dear

[@mohd.saleembhat5658]

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[@hussainbiology]

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[@rimplekour3882]

Well done sir

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✌️🙏

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Nice

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[@hussainbiology]

thanks for appreciation

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[@hussainbiology]

Thanks bro.....

[@TheEatraum]

How is this effected by Deuterium

[@hananerose8669]

Hi what mines a floded three dimensional region of a protein that forms the basic unit of tertiary structure

[@hussainbiology]

unable to understand ur question ??

[@hananerose8669]

@@hussainbiology i found it its domain

[@hussainbiology]

@@hananerose8669 okay great...

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Superb.

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I did like it.

[@hussainbiology]

thanks

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Ty sir

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welcome

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[@madoaj653]

Do u have any website to uppload your pictures?

[@hussainbiology]

No sir

[@KARTAVYA_KR]

I think beta-pleated protein have intermolecular H bonding, by the way nicely presentated.

[@hussainbiology]

Yes....I have only stated intramolecular. BTW thanks for informing what is missing here.

[@lazysuzy32598]

do beta sheets have intra or inter molecular h-bonding please answer

[@hussainbiology]

intermolecular

[@kuldeepsinghshekhawat1389]

Thanx nice explenation of this topic sir but sir esko hindi m explanation dalo na sir plz

[@tahirtantary7438]

Informative

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Thanks Tahir for appreciation....Glad to know that it helps

[@edobenu]

nice

[@hussainbiology]

Thanks Edoardo....

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Impressive

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👌

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when the next vedio I want it, please...

[@qn5595]

👍

[@hussainbiology]

🙏

[@kanicasharma1105]

Sir can we write this process under lipidation??....

[@hussainbiology]

Kanica U can't ,write this for Lipidation...... Lipidation is different process

[@kanicasharma1105]

@@hussainbiology thanks sir.... Btw ur videos are really very helpful....

[@hussainbiology]

@@kanicasharma1105 Thanks KANICA , it really inspires me when i get to know that my work helps,,,,Thanks,,,,Keep sharing and supporting

[@neelujain6807]

Can you plz make vedio in hindi

[@edthoreum7625]

same professor as shomu's biology?

[@hussainbiology]

Yes , like him but i try to make short videos.

[@Lightbulb909]

Polding

[@raginiborkotoky1473]

7:17 what did he say ?

[@hussainbiology]

Proteases launch the attack on Protein , to get away with the protein,.... apologies for my weird pronunciation..... and my speed

[@raginiborkotoky1473]

@@hussainbiology Thankyou. This video was very helpful.

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all are zoology biology students

[@ibrahimansari6753]

Please pronounced occurs correct

[@saramalik5440]

Are u a Kashmiri, prolly from Kupwara

[@hussainbiology]

Yes Kashmiri ( no Bla)

[@saramalik5440]

Yes cud make it from your accent

[@saramalik5440]

I studied from st Joseph’s there

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[@hussainbiology]

Birthyly he totla hai bhai.... Kya kare

[@dr.sayyediliyas1199]

Thank you so much

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Thanks doc for appreciation

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Thanks

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you are welcome....Andrea Keep sharing and supporting

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Thanks for appreciation