Hemoglobin 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.

Globin fold The three-dimensional structure of the proteins that is common to myoglobin and the subunits of hemoglobin. 

Although the amino acid sequences of myoglobin and hemoglobin are homologous, and they adopt the same globin fold, there are important differences in patches where the polypeptide chains in hemoglobin make contact with one... 

Hemoglobins share a common molecular architecture, composed of a polypeptide backbone and an iron porphyrin, as illustrated in Fig. 1. Molecular oxygen binds to the Fe at the center of the planar heme b (Fe protoporphyrin IX). The polypeptide adopts the globin fold constructed primarily from a-helices, customarily labeled with the letters A-H. The heme group binds tightly to a hydrophobic pocket formed primarily from the E- and F-helices. and a bond between the heme Fe and the e-nitrogen of a histidine in the F-helix (His F8) provides the only covalent link between the polypeptide and the heme. 

Fig. 9. Hypothesis on the control of hemoglobin synthesis in chick embryo blastoderm by control of the synthesis of ALA-synthetase. In the nucleus a repressor protein (I) blocks transcription, and a 5jS-H steroid acts as a derepressor, permitting the structural gene (II) to code for the mRNA of ALA-synthetase. In the cytoplasm the information in the mRNA is translated into the enzyme ALA-synthetase (E,) which migrates into the mitochondrion where ALA (III) is made and finally converted by other enzymes (E2-E7) to heme (IV). Heme controls the synthesis of globin either by acting at the initiating site or by permitting proper folding of the globin.

---