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Proteins

Designer Proteins

Although we think of proteins as natural products, scientists are now learning to design proteins. Many of today's designs involve making small changes in already existing proteins. For example, by changing two amino acids in an enzyme that normally breaks down proteins into short peptides, scientists have produced one that instead links peptides together. Similarly, changing three amino acids in an enzyme often used to improve detergents' cleaning power doubled the enzyme's wash-water stability.

Researchers have also designed proteins by combining different naturally occurring domains, and are actively investigating possible applications. Medical applications seem especially promising. For example, we might cure cancer by combining cancer-recognizing antibody domains with the cell-killing domains of diphtheria toxin. While native diphtheria toxin kills many types of cells in the body, scientists hope these engineered proteins will attach to, and kill, only the cancer cells against which their antibody domains are directed.

The long-term goal, however, is to design proteins from scratch. This is extremely difficult today, and will remain so until researchers better understand the rules that govern tertiary structure. Nevertheless, scientists have already designed a few small proteins whose stability or instability helps illuminate these rules. Building on these successes, scientists hope they may someday be able to design proteins for a spectrum of industrial and economic needs.

Resources

Books

Darby, N.J., and T. E. Creighton. Protein Structure. New York: Oxford University Press, 1994.

Gerbi, Susan A. From Genes to Proteins. Burlington, NC: Carolina Biological, 1987.

Yew, Nelson S. Protein Processing Defects in Human Disease. Austin: R. G. Landes, 1994.

Zubay, Geoffrey, and Richard Palmiter. Principles of Biochemistry. Vol. 3. Nucleic Acid and Protein Metabolism. Dubuque, IA: William C. Brown, 1994.

Periodicals

King, Jonathan. "The Unfolding Puzzle of Protein Folding." Technology Review (May/June 1993): 54-61.

Lipkin, Richard. "Designer Proteins: Building Machines of Life from Scratch." Science News 146 (1994): 396-397.

Sato, M., K. Machida, E. Arikado, et al. "Expression of Outer Membrane Proteins of Escherichia coli Growing at Acid pH."" Applied and Environmental Microbiology no. 66 (March 2000): 943-947.

Zhaohui, Xu., J.D. Knafels, and K. Yoshino. "Crystal Structure of the Bacterial Protein Export Chaperone SecB." Nature Structural Biology no. 7 (December 2000): 1172-1177.

W. A. Thomasson

KEY TERMS

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Alpha helix: —A type of secondary structure in which a single peptide chain arranges itself in a three-dimesional spiral.
Beta sheet: —A type of secondary structure in which several peptide chains arrange themselves alongside each other.
Domain: —A relatively compact region of a protein, seperated from other domains by short stretches in which the protein chain is more or less extended; different domains often carry out distinct parts of the protein's overall function.
Messenger ribonucleic acid (mRNA): —A molecule of RNA that carries the genetic information for producing one or more proteins; mRNA is produced by copying one strand of DNA, but is able to move from the nucleus to the cytoplasm (where protein synthesis takes place).
Peptide bond: —A chemical bond between the carboxyl group of one amino acid and the amino nitrogen atom of another.
Polypeptide: —A group of amino acids joined by peptide bonds; proteins are large polypeptides, but no agreement exists regarding how large they must be to justify the name.
Primary structure: —The linear sequence of amino acids making up a protein.
Quaternary structure: —The number and type of protein chains normally associated with each other in the body.
Ribosome: —A protein composed of two subunits that functions in protein synthesis.
Secondary structure: —Certain highly regular three-dimensional arrangements of amino acids within a protein.
Tertiary structure: —A protein molecule's overall threedimensional shape.
Transfer ribonucleic acid (tRNA): —A small RNA molecule, specific for a single amino acid, that transports that amino acid to the proper spot on the ribosome for assembly into the growing protein chain.

Additional topics

Science EncyclopediaScience & Philosophy: Propagation to Quantum electrodynamics (QED)Proteins - What Proteins Do, Protein Structure, Designer Proteins