When a protein folds into its 3D structure (largely dictated by its 1D amino acid (AA) sequence), only the surface residues interact with solvent molecules and ligands dissolved in the solvent surrounding the protein, such as metabolites of various sizes, other proteins, and other biomolecules. This specific presentation of AAs on the protein's surface is characteristic of that protein.
Meanwhile, the AA residues within the protein's interior remain "unseen" and "untouched" by other molecules in the protein's environment (except perhaps when the protein undergoes drastic conformational change/s in response to some stimulus). What are the functions of these "hidden" AA residues? How do they ensure that precisely the right AAs are exposed on the surface at precisely the right spots so that the protein can perform the function it is supposed to do?
One of the strongest forces in the folding of proteins into their native structures is the reduction in free energy resulting from burying hydrophobic amino acid side chains in the interior. That is why most of the residues that are not in contact with the solvent exposed surface of the protein are hydrophobic. Additionally, the formation of salt bridges, hydrogen bonds, and disulfide bonds by other residues in the interior of the protein contribute to the stability of the native structure.
Hi Vicente,
Usually proteins are involved in all sort of conformational changes. Conformational changes could be minor or "drastic". All the interaction with small molecules or other proteins require some conformational changes. Even "relaxed" native conformation does not mean something "rigid", proteins "breath". All this movements small or big are possible thanks to internal structure of proteins. All forces, interactions and factors described in Adam Shapiro's message have one purpose to help residues on the surface properly react on the changes (function, interaction, stress). They do not have to be in proper positions, but they should be able to move to their proper positions.
The way how this could be done may have different solutions. That is why there are proteins with similar function but different folds. It looks like the Nature gave to proteins multiple choices to solve this problem.
So, I would think that "hidden" residues not only place surface AA in "right spots" but give them ability to move to "right spots", if they for some reason were shifted from those positions. They may help to form a new interface to interact with another protein (moving loops, unfolded/refolded helices, building beta sheets). One can imagine this as a team work, some members of the team are exposed, some are "hidden". But everyone is involved in the game.
To Vicente,
When the protein is synthesized by an Ribosome, it is totally exposed to water. Then it will be automatically folding into a final 3D structure. During the folding process, these "untouched or unseen" residues obviously play key roles, which is still an open problem though.
the roles played by amino acid residues in the interior of a folded 3D protein structure are two-fold if these amino acids do not participate in the functions. First thermodynamic stability, second folding mechanisms and stabilisation of the transition state ensembles
- Badges
- Science topic
- Similar topics
- Chemistry
- Biochemistry
- Biomolecules