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As we know that coils and loops are evolutionary variable regions where mutations,deletions, and insertions frequently occur. So does it mean that they don't have much role in the structure of protein? If it so then what are the factors for the protein core structure formation?

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  • $\begingroup$ I think it would be useful in this case to look into instrinsic disordered proteins. Not to say that coil or loop regions have no role in the structure of a protein, but in avoiding the expression of a completely broken construct, protein domains including disordered or linker regions can tolerate mutations of specific types that don't 100% inactivate a critical region. For example, amphipathic residue substitution to another amphipathic residue. The reason we don't see functional valine -> lysine mutations, for example, is they seriously mess up the protein, even from a coil domain. $\endgroup$ – CKM Feb 15 '16 at 23:29
  • $\begingroup$ This is a really big question. Are you asking specifically "How and why do disordered loop regions pack the way they do in protein structure"? $\endgroup$ – James Feb 24 '16 at 6:15
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Firstly, is important to remember that protein structures are dynamic due to the torsion angles between the N-terminal and C-terminal bonds. There are different conformations to expose different sequences to the outside of the protein to react/catalyze. So there is no one perfect conformation for a protein in a biological system.

The best models we have are taken through x-ray crystallography of the crystalized protein structure. This static portrayal of the protein may be inaccurate, because the biological system will expose the protein to different hydrophobic/hydrophilic interactions than the affect of the protein to itself.

Anfinsen's experiments were able to definitively prove the a proteins structure is coded by its amino acid sequence. To answer your question, this sequence is primarily responsible for a protein's core structure formation.

It is still incredibly difficult to predict the structure of a protein using its amino acid sequence. The tertiary structure is a product of salt bridges, hydrogen bonds, hydrophobic forces and polar attractive forces within the molecule (disregarding a proteins possible quaternary structure ). Scientists (from what I believe is Yale, but I may be incorrect), have been trying to find a pattern using computing software for years. As of right now, we cannot purely use amino acid sequence to determine a protein's dynamic structure.

Loops and coils on the outside of proteins because they tend to compose of polar or charged amino acids. Hydrophobic amino acids tend to get pushed towards the center of the protein structure. This occurs because polar residues do not affect affect the entropy of water molecules as much as the nonpolar residues (in the system).

Many deletions/insertions occur during specific transition states that the protein is in. Enzymes actually target specific conformations of a protein that best produces the P product. See image:

Enzyme-substrate coupling

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  • $\begingroup$ Hi and welcome to Bio.SE :) You hit on a really important point about the amino acids fundamentally determine structure. Could you expand on that a little? $\endgroup$ – James Feb 24 '16 at 6:16
  • $\begingroup$ Hi James. I edited my post to elaborate more on amino acid sequence and protein structure. This is still an area of continuing research, so I can not provide a definate answer without the risk of being incorrect. $\endgroup$ – user22087 Feb 24 '16 at 17:18
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Solving the 3D structure of a protein is complex problem. There are multiple layer of informations that come into play.

The first level of organization comes from secondary structure, which is in turn dictated by the AminoAcid sequence. There are common secondary structure motifs such as alpha-elices and beta-sheets. The combination of several 2nd structure motifs will give rise to more complex motifs and eventually to a local 3d structure. This local 3D structure is called a "domain" and is a minimal independent functional unit of a protein, which means it can often be cut out from the rest and retain its function.

Given this overview, the first layer of selection comes from creating 2nd structures which depends on the charge and size of amino acidic residues.

Mutations that destroy the creation of these secondary structure motifs will ultimately have an effect on the final 3d structure.

Loops in a way connect these more rigid motifs and therefore they are less likely to be subjected to evolutionary selection.

However in the end it all ties down to function. If you have a loop within a catalytic site inside a protein, the sequence in the loop will be greatly preserved because size and charge will strongly dictate its interaction with substrates.

Hope this helps.

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