QUATERNARY STRUCTURE OF PROTEINS

• Arrangement of chains in a multichain protein

• Noncovalent association for globular proteins• Covalent association likely for fibrous protens

• Forces: hydrophobic interactions• Association effectively buries large portions of

surface area which would othersise be exposed to an aqueous environment

6.5 How Do Protein Subunits Interact at the Quaternary Level of Structure?

The subunit compositions of several proteins. Proteins with two or four subunits predominate in nature, and many cases of higher numbers exist.

ADVANTAGES OF 4o ASSOCIATION

1. Stability. Surface/volume ratioas complex enlarges and radiusS~r2 while V~r3

Thus favorable protein-protein interactions increase at a greater rate than unfavorable protein-solvent interactions.

2. Exclusion of mutated proteins

ADVANTAGES, CONTINUED

• Efficiency. Small polymerizing units are sythesized more accurately than a single large protein.

• Assembly of catalytic sites is facilitated.• Assembly of units with unique and

coordinated activities is possible, e.g., prolyl hydroxylase α-β subunits

• Cooperativity is possible.

6.5 How Do Protein Subunits Interact at the Quaternary Level of Structure?

Figure 6.42 Isologous and heterologous associations between protein subunits.

6.5 How Do Protein Subunits Interact at the Quaternary Level of Structure?

Figure 6.41 The quaternary structure of liver alcohol dehydrogenase.

6.5 How Do Protein Subunits Interact at the Quaternary Level of Structure?

Figure 6.43 Many proteins form tetramers by means of two sets of isologous interactions. The tetramer of transthyretin is formed by isologous interactions between the large β-sheets of two transthyretin dimers.

6.5 How Do Protein Subunits Interact at the Quaternary Level of Structure?

Figure 6.44 Multimeric proteins are symmetric arrangements of asymmetric objects. A variety of symmetries is displayed in these multimeric structures.

6.5 How Do Protein Subunits Interact at the Quaternary Level of Structure?

Figure 6.45 Schematic drawing of an immunoglobulin molecule, showing the intermolecular and intramolecular disulfide bonds.

Open Quaternary Structures Can Polymerize

Figure 6.46 The structure of a typical microtubule, showing the arrangement of the α- and β-monomers of the tubulin dimer.

6.5 How Do Protein Subunits Interact at the Quaternary Level of Structure?

Figure 6.42 Isologous and heterologous associations between protein subunits.

TOBACCO MOSAIC VIRUS

• EM: 3000 Ao long, 180 Ao in diameter

• 2130 identical protein subunits assemble around a single RNA strand

AN ENZYME COMPLEX

The pyruvate dehydrogenase complex carries out the following reaction

Pyruvate + CoA + NAD+ acetylCoA + C02 + NADH

Three enzymatic activities are needed to carry out this reaction. These are done in a complex of multiple copies of these 3 enzymes

Figure 19.4 The Reaction Mechanism of the Pyruvate Dehydrogenase Complex

Decarboxylation of pyruvate yields hydroxyethyl-TPP. Transfer to lipoic acid is followed by formation of acetyl-CoA.

Pyruvate Dehydrogenase is a Multi-Subunit Complex of Three Enzymes

Figure 19.3 Icosahedral model of the pyruvate dehydrogenase complex (PDC) core structure. E1 subunits are yellow; E2 subunits are green. Linkers in blue; E3 not shown.

Distribution of RNA and protein on the chloro-ribosome with positions of PSRPs and PRP extensions highlighted.

Sharma M R et al. PNAS 2007;104:19315-19320

©2007 by National Academy of Sciences

Hemoglobin, which consists of two a and two b polypeptide chains, is an example of the quaternary level of protein structure. In this drawing, the b-chains are the two uppermost polypeptides and the two a-chains are the lower half of the molecule. The two closest chains (darkest colored) are the b2-chain (upper left) and the a1-chain (lower right). The heme groups of the four globin chains are represented by rectangles with spheres (the heme iron atom). Note the symmetry of this macromolecular arrangement.

The structure of myoglobin is similar to that of the Hb monomer

Figure 15.21 The myoglobin and hemoglobin structures.

Myoglobin is monomeric

Hemoglobin is tetrameric

Figure 15.20 O2-binding curves for hemoglobin and myoglobin

FIBRIN FIBERSMolecules offset by 23 nm

• Fibers stabilizing blood clots

Things to Know

• Stability: reduction of surface to volume ratio • Genetic economy and efficiency • Bringing catalytic sites together • Cooperativity