Heg. Aronson et al., QUANTIFICATION OF TERTIARY STRUCTURAL CONSERVATION DESPITE PRIMARY SEQUENCE DRIFT IN THE GLOBIN FOLD, Protein science, 3(10), 1994, pp. 1706-1711
The globin family of protein structures was the first for which it was
recognized that tertiary structure can be highly conserved even when
primary sequences have diverged to a virtually undetectable level of s
imilarity. This principle of structural inertia in molecular evolution
is now evident for many other protein families. We have performed a s
ystematic comparison of the sequences and structures of 6 representati
ve hemoglobin subunits as diverse in origin as plants, clams, and huma
ns. Our analysis is based on a 97-residue helical core in common to al
l 6 structures. Amino acid sequence identities range from 12.4% to 42.
3% in pairwise comparisons, and, despite these variations, the maximal
RMS deviation in alpha-carbon positions is 3.02 Angstrom. Overall, se
quence similarity and structural deviation are significantly anticorre
lated, with a correlation coefficient of -0.71, but for a set of struc
tures having under 20% pairwise identity, this anticorrelation falls t
o -0.38, which emphasizes the weak connection between a specific seque
nce and the tertiary fold. There is substantial variability in structu
re outside the helical core, and functional characteristics of these g
lobins also differ appreciably. Nevertheless, despite variations in de
tail that the sequence dissimilarities and functional differences impl
y, the core structures of these globins remain remarkably preserved.