The Three-dimensional Structure of Proteins is More Highly Conserved than the Primary Structure

* The 3D structure is stabilized by a multitude of specific interactions between the various chemical groups present.

* If the differences between two homologous species are examined, a general tendency is observed for chemically similaramino acid residues to be found at the same position.

The substitution of one acidic residue (e.g. Glu for Asp) is likely to be of less consequence to the interactions with nearby residues than would the substitution of Glu for Val.

* This tendency is summarized in this Dayhoff Matrix.

Mutations to dissimilar residues are more likely to lead to the 3D conformation being less stable, or even to the inability of the mutant polypeptide chain to ever fold.

1. In such cases, the function of the protein is therefore impaired or disabled, which is likely to disadvantage the organism to some degree or other.

2. Such mutations tend to be lost from the population; they are selected against, while the 'neutral', or even advantageous, mutations persist (are 'fixed').

3. Some mutations would be expected to be favourable, by altering the 3D structure such that it functions more efficiently.

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Homologous proteins have similar 3D structures

- the differences in primary structure do not result in a drastic rearrangement of the folded conformation. If they did, they would in most cases disappear from the population.

Relative scale of conservation of structure is as follows: