Globin chains

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 9.5. Attachment of the haem group to the globin chain via a coordinated histidine group.

Circulating RBCs lack the enzymes to produce either haem groups or globin chains so the synthesis of haemoglobin is a defining feature of early RBC maturation. Globin chain production is like the formation of any other protein, but a and 3 chain synthesis is closely linked with haem synthesis. 

Fig. 1. Tertiary structure of globin chain, showing helical and nonhelical segments and the position of the heme.

Underproduction of -globin chains in -thalassemia leads to an excess of a chains, which can form... 

Sickle hemoglobin (HbS) differs from normal adult hemoglobin (HbA) at amino acid number 6 of the P-globin chain, where HbS has a Val and HbA a Glu. 

Several variants of -thalassemia are caused by nonsense mutations leading to production of truncated, unstable 3-globin chains. 

Basis of the Sickle-Cell Mutation Sickle-cell hemoglobin has a Val residue at position 6 of the j3-globin chain, instead of the Glu residue found in normal hemoglobin A. Can you predict what change took place in the DNA codon for glutamate to account for replacement of the Glu residue by Val ... 

Two copies of the a-globin gene are designated a1 and o2. Each can provide a-globin chains that combine with p-globin chains. 

Each copy of ChrOiuusoiue 11 has only one gene for p-globin chains. 

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