Question

Amino acid sequence analysis of all of the peptides found in a single IgG antibody would reveal unique peptide sequences totaling ~600-700 amino acids. Using

this estimate, the predicted molecular weight of an antibody protein would be ~70-75 kDa. Yet, an intact antibody protein has a molecular weight of ~150 kDa. The explanation for this discrepancy is:

A. IgG antibodies have many more heavy amino acids in them than most other proteins.
B. Each IgG antibody is a complex of two identical light chains and two identical heavy chains.
C. IgG antibodies tend to aggregate together during purification, thereby distorting molecular weight estimates.
D. Each IgG antibody is a complex of four identical polypeptides.
E. IgG antibodies are produced as dimers of two identical IgG monomers

Answer 1

The discrepancy between the predicted and actual molecular weight of an IgG antibody is due to the fact that an IgG molecule is a complex made up of two identical light chains and two identical heavy chains, not a monomer, resulting in a larger molecular weight of about 150 kDa.

Step-by-step explanation:

You may have noticed a discrepancy between the estimate of the size of an IgG antibody based on amino acid sequence analysis and the actual molecular weight of an intact IgG antibody molecule. The estimate of 600-700 amino acids would predict a protein of ~70-75 kDa, given that the average molecular weight of an amino acid is 110 Da. However, the true molecular weight of an intact antibody is about 150 kDa.

This apparent discrepancy is because an IgG antibody is not a monomer but a complex of two identical light chains and two identical heavy chains (L₂H₂). Each light chain comprises about 214 amino acids, whereas each heavy chain is composed of approximately 446 amino acids. Together, these produce a structure with a molecular weight of roughly 150 kDa. The light chains possess the VL (variable light) and CL (constant light) regions, while heavy chains have the VH (variable heavy) and CH1, CH2, and CH3 (constant heavy) regions.

Answer 2

The ~150 kDa molecular weight of an intact IgG antibody is due to its structure of two identical heavy chains and two identical light chains, not the peptide sequences alone.B is the correct answer.

Step-by-step explanation:

The discrepancy in the molecular weight between predicted and actual size of an IgG antibody can be explained by its quaternary structure. Each IgG antibody is a complex of four polypeptide chains: two identical light chains and two identical heavy chains. These chains are held together by disulfide bonds in a "Y" formation, which collectively contribute to the molecular weight of approximately 150 kDa.

The light chains consist of about 214 amino acids, while the heavy chains are composed of 446 amino acids. Given that the average molecular weight of an amino acid is 110, the tally for the entire antibody protein reflects the contributions of all four chains. Thus, while the analysis of peptides reveals sequences totaling about 600-700 amino acids, the presence of two heavy and two light chains accounts for the intact antibody's molecular weight.

The correct option to explain the observed molecular weight is option B: "Each IgG antibody is a complex of two identical light chains and two identical heavy chains."