Globin fold

Hemoglobin is a tetramer built up of two copies each of two different polypeptide chains, a- and (5-globin chains in normal adults. Each of the four chains has the globin fold with a heme pocket. Residue 6 in the p chain is on the surface of a helix A, and it is also on the surface of the tetrameric molecule (Figure 3.13). 

Figure 3.13 The hemoglobin molecule is built up of four polypeptide chains two a chains and two (3 chains. Compare this with Figure 1.1 and note that for purposes of clarity parts of the a chains are not shown here. Each chain has a three-dimensional structure similar to that of myoglobin the globin fold. In sicklecell hemoglobin Glu 6 in the (3 chain is mutated to Val, thereby creating a hydrophobic patch on the surface of the molecule. The structure of hemoglobin was determined in 1968 to 2.8 A resolution in the laboratory of Max Perutz at the MRC Laboratory of Molecular Biology, Cambridge, UK.

We thus have here a case where a mutation on the surface of the globin fold, replacing a hydrophilic residue with a hydrophobic one, changes important properties of the molecule and produces a lethal disease. Why has the... 

The globin fold has been used to study evolutionary constraints for maintaining structure and function. Evolutionary divergence is primarily constrained by conservation of the hydrophobicity of buried residues. In contrast, neither conserved sequence nor size-compensatory mutations in the hydrophobic core are important. Proteins adapt to mutations in buried residues by small changes of overall structure that in the globins involve movements of entire helices relative to each other. 

Figure 4.11 (a) Four helix bundle domain proteins, illustrated by myohaemerythrin. The oxygenbinding site is located at the di-iron centre within the hydrophobic core of the helical bundle, (b) The globin fold, represented here by myoglobin. (From Branden and Tooze, 1991. Reproduced by permission of Garland Publishing, Inc.)... 

Answer Myoglobin is all three. The folded structure, the globin fold, is a motif found in all globins. The polypeptide folds into a single domain, which for this protein represents the entire three-dimensional structure. 

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