Biochemistry - Chemical Reactions in Living Cells, Volume 1 - D. Metzler 1980

How molecules interact with one another
Macromolecular packing
Oligomers containing different types of subunits

Many Enzymes, viral capsids, and more complex molecular structures are built from protomers of two or more types. Hemoglobin has been studied in the most detail; it is a tetrameric protein (a₂β₂) composed of two similar, yet non-identical subunits, a and ß (both having a mol. weight of 16,100). Although the Amino acid sequences of the subunits differ significantly, the folding of The polypeptide chains in both hemoglobin subunits is nearly identical (and very similar to that in monomeric Myoglobin) [56]. Were it not for these differences, the hemoglobin molecule would be highly symmetrical, featuring the type of interactions shown in Fig. 4-9, B, and three 2-fold axes of Symmetry. It is customary to say that the hemoglobin molecule possesses one true 2-fold axis of symmetry and two pseudo-2-fold axes. It contains two sets of purely isologous interactions (between the two a-subunits and the two ß-subunits) and two pairs of heterologous interactions (between the a- and ß-subunits). The exquisite illustrations by Dickerson and Geis [57] clearly reveal the nearly symmetrical orientation of the various segments of the polypeptide chain.

The contact between the subunits of one pair (a₁ß₁) is somewhat stronger than that of the other. In the former case, the side chains of 34 amino acid residues and a total of 110 atoms are in close contact with one another [55]. Hydrophobic interactions make the primary contribution to the forces holding the subunits together, while the number of contacts similar to those occurring in purely isologous binding is quite small. The interaction of the other subunit pair, a₁ß₂, involves only 19 amino acid residues and a total of just 80 atoms. Because this contact is weaker than the first, hemoglobin dissociates relatively easily into aß-dimers, where the subunits are held together by a₁ß₁ contacts, whereas their relative movements during oxygenation take place in the region of the a₁ß₂ contacts (Sec. D.5.a). Truly isologous contacts (i.e., aa and ßß) are weak because identical protomers are sterically incompatible with each other.

Aspartate transcarbamoylase (mol. weight = 310,000), an enzyme isolated from E. coli, can dissociate into two trimers, commonly referred to as catalytic subunits (mol. weight of the trimer is 100,000), and three dimers, called Regulatory Subunits (mol. weight of the dimer is 34,000). The molecule of this enzyme resembles a triangular plate in shape [58, 59], with a thickness of 9.2±1.0 nm and a side length of 10.5±1.0 nm. It possesses 3:2 symmetry, meaning it is a dihedral Structure with one 3-fold axis of symmetry and three 2-fold axes. The two trimers and the dimeric subunits positioned between them appear to be arranged “back-to-back”; the latter are tightly packed in the grooves running along the edges of the trimers. The dimers are not arranged strictly parallel to the 3-fold axis of symmetry: to avoid steric clashes, the upper and lower halves are rotated relative to each other around the 3-fold axis of symmetry. In the center, There is a Water-filled cavity measuring ~2.5x5.0x5.0 nm. The active sites of the enzyme are apparently located inside this cavity, which can be accessed through six 1.5 nm-diameter openings situated on the sides of the structure.

Many other oligomeric enzymes and various complex structures are known to contain protein subunits of more than one type. Examples include a-keto acid dehydrogenases, which are massive, cube-shaped complexes with a mol. weight of ~2–4 million, containing three different Proteins (Fig. 8-18). Skeletal Muscle fibers (Sec. E), Antibodies (Supplement 5-E), Blood Complement (Supplement 5-F), and the strikingly shaped tailed bacteriophage (Supplement 4-D) are all exceptionally complex and elegant molecular structures.