Overview

Proteins are the molecular machines at the heart of life. Capable of moving muscles, digesting food, and informing the brain about stimuli as diverse as the light bouncing off of a beautiful painting or the chemicals wafting up from a rotting corpse, proteins are essential to nearly every action performed by a modern day cell. According to the basic dogma of molecular biology, DNA¹ can be transcribed into RNA which is then translated into amino acid chains. These chains can then fold into the functional proteins used by the cell. ²

Transcription

The blueprints, or genes, for a cell's proteins are contained in its DNA³. Each double-helical DNA molecule consists of two long sugar-phosphate backbones to which are attached, like charms on a charm bracelet, four different types of nitrogenous bases: guanadine (G), cytosine (C), adenosine (A), and thymadine (T). Through hydrogen bonds, the bases on one strand of a DNA molecule are able to form specific pairs with the bases on the other strand, G pairing with C and A pairing with T. Because of this specific pairing, the sequence of the bases on any strand reflects the sequence of its complementary strand. For example, if one strand contains the sequence TCAGACGAGGAGGTC, the other strand must contain the sequence GACCTCCTCGTCTGA. This complimentarity allows the blueprint for each protein to be reproduced on new strands of DNA each time the cell divides. Some of these blueprints are constantly being read by the cell (constituitively expressed), while others are read only at specific times, by specific cell types, or in response to specific signals.

When a gene is in an active, "readable" state, a protein complex called RNA polymerase can make single stranded RNA copies of the original DNA sequence of the gene. Like DNA, a strand of RNA contains a sugar-phosphate backbone to which four different types of nitrogenous bases are attached. RNA contains the base uracil (U) instead of thymadine; however, since U is very similar to T, lacking only one methyl group, RNA is able to form U-A base pairs analogous to the T-A base pairs in DNA. RNA polymerase makes use of RNA's ability to form specific base pairs with DNA to make its messenger RNA copies. For example, if the original gene for a protein contains the sequence TCAGACGAGGAGGTC, its complimentary strand will contain the sequence GACCTCCTCGTCTGA and its initial RNA transcript will contain the sequence GACCUCCUCGUCUGA.⁴

Translation

Finally, an RNA/protein complex called the ribosome builds a protein, a chain of amino acids, based on the blueprint in the messenger RNA. In most organisms, the blueprint is translated based on the "universal" genetic code. The molecular basis for this code lies in transfer RNA, RNA molecules that are transcribed in the same manner as messenger RNA but which, instead of being read as messages, can fold independently into "L" shaped structures. One arm of the "L" contains an "anticodon" loop which displays three bases specific to the transfer RNA. Since there are four different types of bases that can occur in the anticodon (U,A,G, and C), there are 4x4x4=64 possible anti-codons. 61 of these possible anti-codons are found in transfer RNAs. Proteins called aminoacyl-tRNA synthases can recognize specific transfer RNAs and attach one of twenty amino-acids to the other "arm" of the "L". Because of the specificity of the aminoacyl-tRNA synthases, each anti-codon will always be associated with the same amino acid. Therefore, by allowing three-base "codons" in the messenger RNA to pair in a specific fashion with their corresponding anticodons in
transfer RNA, ribosomes are able to translate a specific RNA sequence into a speficic amino acid sequence (for example, the RNA sequence GACCUCCUCGUCUGA is translated into the amino acid sequence serine-aspartate-glutamate-glutamate-valine in the nuclei of most cells). As each transfer RNA arrives at the ribosome, its amino acid is removed and added to the growing amino-acid chain that will become the protein. This process is terminated when the ribosome arrives at a "stop" codon in the messenger RNA, one of the three codons for which there is no transfer RNA containing the corresponding anticodon. These stop codons are recognized by release factors, which cause the ribosome to release the newly synthesized protein.⁵

Each of the twenty⁶ amino acids encoded by the "universal" code has unique structural and chemical properties, distinct preferences for certain three dimensional conformations, for certain interactions with other amino acids. Based on the particular combination of properties the protein derives from its component amino acids, a given protein will be able to adopt certain three-dimensional folded shapes⁷, to catalyze specific chemical reactions, and to interact with other proteins--in effect, to become one of many microscopic machines carrying out the tasks vital to this thing we call life.

"Genes VI" by Benjamin Lewin, Oxford University Press, Inc., New York 1997
"Biochemistry" by Donald and Judith Voet, John Wiley & Sons, Inc., New York 1995
"Molecular Biology of the Cell" by Bruce Alberts, Dennis Bray, Julian Lewis, Martin Raff, Keith Roberts, and James
Watson, Garland Publishing, New York, 1994

The Lewin book is written from a molecular biologist's point of view, Voet & Voet focus more on the biochemistry, and Alberts et al. features a cell biologist's point of view as well as a picture of the authors walking across Abbey Road on the back cover.