Question

In the human genetic disease sickle cell anemia, a single change in the genetic sequence of the hemoglobin-beta gene results in the amino acid valine being substituted for the amino acid glutamic acid in the beta chain of the hemoglobin protein. Which level(s) of the protein structure will be affected?

Answer 1

Answer-

According to the given question-

• Sickle cell anemia is a condition where individuals develop abnormal red blood cells.
• It is an inherited , recessive disorder , due to mutation in gene called HBB or haemoglobin beta found on chromosome number 11.
• haemoglobin is a heterotetramer protein with two α-globin and β-globin subunits joined through non-covalent , having heme group with iron which is bivalent , found in red blood cells responsible for carrying oxygen inside the body .
• α globin genes and β globin genes are found on chromosomes number 16 and 11, respectively,
• DNA present on chromosome 11 , leads to mutation of gene at sixth codon responsible for synthesizing β globin,causes replacement of adenine nitrogen base present in codon GAG by base thymine present in codon GTG leads to glutamic acid substitution with valine at the position 6 from β) chain with N-terminal end and leads to formation of Hb S or hemoglobin S , the protein having two normal α-chains but with abnormal or mutant β- chains in the form of α2A β2S.
• This causes changes at several level such as molecular level , cellular level, tissue level as well as inside the organism also.
• isoelectric points of glutamic acid is 5.97 while valine have 2.77 this leads to loss of negative charges present in HbA compared to Hb S because glutamic acid have negative charge while valine are hydrophobic and leads to physical structure of hemoglobin molecule and also affect the activity during loading of oxygen .
• This also leads to formation of hydrogen bonds between the valine present in same globin and promote intermolecular interaction between several amino acid such as GLU121--> GLY16, as well as ASP73--> THR4, and this leads to formation of polymer of Hb S .
• There is also hydrophobic interactions between amino acid valine present in beta chain at 6 and the amino acid present in hydrophobic concavity such as leucine88 as well as phenylalanine85 in Hb S polymers .

So due to amino acid substitution of glutamic acid through valine there is change in primary, secondary , tertiary as well as quaternary structure of hemoglobin occur which affect its shape, their interaction as well as function..