Tertiary Quaternary Structure

The term "tertiary structure" refers to the entire three-dimensional conformation of a polypeptide. It indicates, in three-dimensional space, how secondary structural features—helices, sheets, bends, turns, and loops— assemble to form domains and how these domains relate spatially to one another. A domain is a section of protein structure sufficient to perform a particular chemical or physical task such as binding of a substrate

COOH

kCH2OH

Figure 5-7. A p-turn that links two segments of antiparallel p sheet. The dotted line indicates the hydrogen bond between the first and fourth amino acids of the four-residue segment Ala-Gly-Asp-Ser.

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Figure 5-6. Examples of tertiary structure of proteins. Top: The enzyme triose phosphate isomerase. Note the elegant and symmetrical arrangement of alternating p sheets and a helices. (Courtesy of J Richardson.) Bottom: Two-domain structure of the subunit of a homodimeric enzyme, a bacterial class II HMG-CoA reductase. As indicated by the numbered residues, the single polypeptide begins in the large domain, enters the small domain, and ends in the large domain. (Courtesy of C Lawrence, V Rodwell, and C Stauffacher, Purdue University.)

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Figure 5-6. Examples of tertiary structure of proteins. Top: The enzyme triose phosphate isomerase. Note the elegant and symmetrical arrangement of alternating p sheets and a helices. (Courtesy of J Richardson.) Bottom: Two-domain structure of the subunit of a homodimeric enzyme, a bacterial class II HMG-CoA reductase. As indicated by the numbered residues, the single polypeptide begins in the large domain, enters the small domain, and ends in the large domain. (Courtesy of C Lawrence, V Rodwell, and C Stauffacher, Purdue University.)

or other ligand. Other domains may anchor a protein to a membrane or interact with a regulatory molecule that modulates its fUnction. A small polypeptide such as triose phosphate isomerase (Figure 5-6) or myoglobin (Chapter 6) may consist of a single domain. By contrast, protein kinases contain two domains. Protein kinases catalyze the transfer of a phosphoryl group from ATP to a peptide or protein. The amino terminal portion of the polypeptide, which is rich in P sheet, binds ATP, while the carboxyl terminal domain, which is rich in a helix, binds the peptide or protein substrate (Figure 5-8). The groups that catalyze phosphoryl transfer reside in a loop positioned at the interface of the two domains.

In some cases, proteins are assembled from more than one polypeptide, or protomer. Quaternary structure defines the polypeptide composition of a protein and, for an oligomeric protein, the spatial relationships between its subunits or protomers. Monomeric proteins consist of a single polypeptide chain. Dimeric proteins contain two polypeptide chains. Homodimers contain two copies of the same polypeptide chain, while in a heterodimer the polypeptides differ. Greek letters (a, P, Y etc) are used to distinguish different sub-units of a heterooligomeric protein, and subscripts indicate the number of each subunit type. For example, a4 designates a homotetrameric protein, and a2P2Y a protein with five subunits of three different types.

Since even small proteins contain many thousands of atoms, depictions of protein structure that indicate the position of every atom are generally too complex to be readily interpreted. Simplified schematic diagrams thus are used to depict key features of a protein's ter-

Figure 5-8. Domain structure. Protein kinases contain two domains. The upper, amino terminal domain binds the phosphoryl donor ATP (light blue). The lower, carboxyl terminal domain is shown binding a synthetic peptide substrate (dark blue).

tiary and quaternary structure. Ribbon diagrams (Figures 5-6 and 5-8) trace the conformation of the polypeptide backbone, with cylinders and arrows indicating regions of a helix and P sheet, respectively. In an even simpler representation, line segments that link the a carbons indicate the path of the polypeptide backbone. These schematic diagrams often include the side chains of selected amino acids that emphasize specific structure-function relationships.

MULTIPLE FACTORS STABILIZE TERTIARY & QUATERNARY STRUCTURE

Higher orders of protein structure are stabilized primarily—and often exclusively—by noncovalent interactions. Principal among these are hydrophobic interactions that drive most hydrophobic amino acid side chains into the interior of the protein, shielding them from water. Other significant contributors include hydrogen bonds and salt bridges between the carboxylates of aspartic and glutamic acid and the oppositely charged side chains of protonated lysyl, argininyl, and histidyl residues. While individually weak relative to a typical covalent bond of 80-120 kcal/mol, collectively these numerous interactions confer a high degree of stability to the biologically functional conformation of a protein, just as a Velcro fastener harnesses the cumulative strength of multiple plastic loops and hooks.

Some proteins contain covalent disulfide (S —S) bonds that link the sulfhydryl groups of cysteinyl residues. Formation of disulfide bonds involves oxidation of the cysteinyl sulfhydryl groups and requires oxygen. Intrapolypeptide disulfide bonds further enhance the stability of the folded conformation of a peptide, while interpolypeptide disulfide bonds stabilize the quaternary structure of certain oligomeric proteins.

THREE-DIMENSIONAL STRUCTURE IS DETERMINED BY X-RAY CRYSTALLOGRAPHY OR BY NMR SPECTROSCOPY

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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