AMINO ACIDS, POLYPEPTIDES AND PROTEINS

Transcription

1 AMINO ACIDS, POLYPEPTIDES AND PROTEINS As mentioned above, some of the simplest and most stable forms of nucleic acid to be produced were the transfer RNA molecules - probably at random at first but later by specific catalytic mechanisms. Every single cell in our bodies and in every other living organism contains about 20 of these structures, one for each natural aminoacid of the type shown below. These transfer RNA molecules bind a specific amino acid to the terminal adenosine (A) end and have a specific sequence of three nucleosides (the triplet code) on the loop at the other end. In other words, they attach a specific three-letter code to each amino acid. The transfer RNA triplet code for phenylalanine is AAA, for serine, AGA, for leucine, GAG. As you can see in the chart above, each amino acid has a unique structure but they all contain the same CO2 (acid) and N (amine) so they can be attached together, as shown below, to form long polypeptide chains, sometimes composed of thousands of peptide units, all arranged in specific sequences. 1

2 Each peptide in a chain serves a unique role relative to water adjacent to it. Those with positively and negatively-charged side-chains attract each other and transfer charges linearly through adjacent water. Lipophilic, hydrocarbon groups order water adjacent to them; they repel water away from them and associate as closely as possible with other hydrocarbon, lipid regions. Sections containing small aminoacids like glycine, serine and proline, bind water molecules on all sides, disrupt linear hydration order and are extremely mobile. Polypeptide segments with charged or hydrocarbon side chains often produce straight beta-sheet or helical coil regions but sequences of two or more small peptides usually cause chains to change direction in beta turns while segments with a number of the small peptides have the freedom to coil in space and permit beta-sheet and coiled regions to find close packing arrangements to bring opposite charges together and permit lipid, water-ordering regions to fit tightly together. Although many of the amino acids involved in current polypeptide syntheses can be produced by subjecting ammonia and the gaseous components in the atmosphere to electrical discharges, we really do not know how they were formed originally possibly on crude nucleic acid enzymes. What we do know is that polypeptides of the type shown above were not formed simply by heating the amino acids. Heating amino acids does not produce polypeptides, it simply converts them into cyclic molecules, most of which are not found in nature. Thus, it is likely that the formation of biochemicals on earth passed through four stages: sugars and polysaccharides, nucleosides and nucleic acids, polypeptides and proteins and, as we will see later, fatty acids and membranes. However, the synthesis of functional polypeptides was much more complex than that of the polymers before them. 2

3 Random synthesis of polypeptides may have occurred periodically prior to the development of functional nucleic acids but it was not until structurally-stable nucleic acids were available which could catalyze the attachment of specific amino acids to the ends of transfer RNA molecules could specific sequences of amino acids in polypeptides be produced. One of the unique features of the transfer RNA molecule is that the loop with the tripletcoded is flat, it permits two molecules to lay side-by-side with their triplet codes bound to adjacent complimentary codes on a single linear strand of (messenger) RNA as shown below. If, now, the amino acids attached to the other end were brought close together by lying on another RNA surface, the amino acid on the second molecule could bond with that of the first and a dipeptide could be formed. Coupling one aminoacyled t-rna after another to their complimentary codes on m-rna s would have yielded coded polypeptides. Once nucleic acid surfaces were available which could produce a variety of aminoacyled t- RNA molecules and hold them together on segments of messenger RNA, the synthesis of specific sequences of polypeptides must have proceeded at a relatively rapid rate. Obviously, we do not know what the nucleic acids looked like that performed these first catalytic functions but we do know that nucleic acid segments which hold them together today might well have been very similar to, if not identical, to those in early forms. 3

4 At first, there was probably little selectivity for amino acids and dry heating might have provided energy for the attachment of the amino acids to the transfer RNAs. However, once aminoacylated transfer RNAs began to form, their relatively flat structures must have permitted them to produce a tremendous variety of polypeptides. Once again, those that could wrap to form stable functional units survived, those that could not were hydrolyzed back to aminoacids. Since the reactions were not catalyzed well, they most likely were extremely slow and with a tremendous variety of sequences produced for millions of years. However, it is likely that some of the first polypeptides to be produced bound to the RNA molecules which had produced them. Some of them blocked further synthesis; others provided improved stability and functionality. As the size and stability increased, some nucleic acid complexes became more efficient - those are the ones that have survived and become the critical functional parts of the huge ribosomal particles that exist today. Although ribosomal particles in living cells today are large enough to be seen with a microscope, nucleotide sequences that bind messenger RNAs (mrnas) and aminoacyl transfer RNAs (Aa-tRNAs) today might very well be the same as those that produced the first polypeptides. Today, ribosomes are composed of 3 long nucleic acids and 55 proteins. The proteins are primarily on the outer surfaces - they control the beginning and end of syntheses, provide ATP power to draw m-rnas through the complex and fill voids in surfaces to remove water, increase structural stability and improve control in coding and production of correct sequences of polypeptides. In ribosomes today, a single strand of m-rna is drawn by ATP power across a nucleic acid platform in Particle A which holds two adjacent Aa-tRNAs so that their triplet codes perfectly match complimentary codes on the mrna strand. Once the amino acids are attached together in particle B, the resulting polypeptide chain passes down a channel in B. As polypeptides emerge into the aqueous environment they immediately begin wrapping to produce functional proteins. Sometimes, chaperone proteins bind to newly-formed polypeptides as they exit particle B and help them wrap into their lowest energy forms but it is the sequence of peptides in the chain, their interaction with each other and with linearizing surface water that determines the final protein structure. 4

5 In spite of the structural complexity of these huge ribosomes, if heated in an aqueous ionic medium similar to that in the cell, they separate into the 3 nucleic acids and the 55 polypeptide parts. On cooling, they spontaneously assemble, once again, to form the original, functional particles. It is absolutely amazing that all nucleic acids and all polypeptides in living cells have the capacity to spontaneously assemble into their functional forms. However, if the medium is denatured, by leaving out critical salts or by adding additional salts or liquids like alcohol, the linearizing property of water is disrupted, spontaneous wrapping does not occur and molecular messes are produced. Thus, the saline medium, with its dynamic linearizing and ordering properties, systematically directs surface charges into close association and hydrophobic, hydrocarbon regions into close proximity to produce unique, geometric functional forms. As mentioned before, the insulin molecule, which is produced in pancreatic cells as a single polypeptide segment, spontaneously wraps into coiled sections that associate together to exclude water from the central region and form stable structural units. Once the assembly is complete, section C, which contains a number of small, hydrating glycine peptides, is clipped off enzymatically to give the functional insulin molecule. As you can see, the final molecule, like the transfer RNA molecule discussed above, has a geometry that fits into the linearizing environment of water around it. This provides for improved stability and functionality as it binds to complimentary linearly-ordered sites in cell membranes to promote the uptake of glucose into cells. 5