Fundamentals of Molecular Biology. Part 1: Molecular Cell Biology - A. N. Ogurtsov 2011

Molecular Principles of Protein Function
Protein Families

Studies of Myoglobin and Hemoglobin—Proteins that transport oxygen in Muscles and Blood, respectively—have demonstrated that Protein Functions are determined by their three-dimensional Structure, which, in turn, is dictated by the Amino Acid Sequence, or Primary Structure.

X-ray crystallography has revealed that the three-dimensional structures of myoglobin and the a and ß subunits of hemoglobin are strikingly similar (Figure 119). Subsequent sequencing of myoglobin and hemoglobin subunits showed that many identical or chemically similar residues occupy identical positions in the primary structures of both proteins.

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Figure 119 - Tertiary Structure of homologous globins

Similar comparisons of other proteins have conclusively confirmed that amino acid sequence, three-dimensional structure, and protein function are intimately interconnected and interdependent.

Today, this principle is widely applied in Proteomics to predict the Structure and function of newly discovered proteins by comparing their Amino acid sequences with those of proteins whose structures and functions are already established.

The Use of such database searches continues to expand as the complete genomes of an increasing number of organisms are fully sequenced.

Based on the comparison of protein molecular structures, a novel scheme of biological Classification has been developed, grounded in the Similarities and differences of protein amino acid sequences.

Proteins that share a common ancestral precursor are termed homologous. The primary indicator of protein Homology—and thus of a common ancestor—is the similarity of their amino acid sequences and structures.

Homologous proteins are said to belong to the same family. Comparing their structures allows us to reconstruct their evolutionary Lineage. The three-dimensional structures of homologous proteins remain similar even when significant divergence is observed in their primary structures.

The evolutionary relationships among homologous proteins are most clearly illustrated as a Phylogenetic Tree. For example, The amino acid sequences of globins from Bacteria, plants, and animals demonstrate that they descended from a common ancestor—a monomeric oxygen-binding protein (Figure 120).

Over time, the genes encoding the ancestral globin protein gradually evolved as the PLANT AND ANIMAL lineages diverged. Further modifications led to The Emergence of myoglobin, a monomeric Muscle oxygen-binding protein, and the a and ß subunits of the tetrameric hemoglobin molecule (a₂ß2) of the Circulatory system. In all these globins, a non-covalently bound heme molecule serves as the oxygen-binding site.

Figure 120 - Phylogenetic tree of globins