Protein Synthesis

Protein Synthesis

A gene is the basic unit of heredity in a living organism • All living things depend on genes • Genes hold the information to build and maintain their cells and pass genetic traits to offspring • the term gene often refers to the scientific concept of an allele. • A sequence of nucelotides in DNA that performs a specific function such as coding for a particular protein

Complex molecules (macromolecules) composed of one or more polypeptide chains • Polypeptide chains are made of amino acids and folded into specific 3D shapes • The 3D shape determines protein function • DNA is a polymer made up of nucleotides • Protein is a polymer made up of amino acids

The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code

1909- Archibald Garrod, a British physician • Proposed the relationship between genes and proteins • One gene directs the production of one enzyme • He observed that inherited diseases reflect a patient's inability to make a particular enzyme

Worked with patients having Alkaptonuria • Alkaptonuria- a genetic disorder in which urine appears black because it contains the chemical alkapton • When exposed to air, alkapton darkens in color • His analysis showed that alkapton was present in high concentration in people who had the disorder • He hypothesized that a defective enzyme causes an “inborn error of metabolism”

Intermediary Metabolites Initial Reactant Final Product A B C D Enzyme 1 Enzyme 2 Enzyme 3 Biochemical reactions are controlled by enzymes Enzymes are often are organized into chains of reactions known as metabolic pathways. Loss of activity in a single enzyme can inactivate an entire pathway. He hypothesized that a defective enzyme causes an "inborn error of metabolism“ If there is an accumulation of substance B, then enzyme 2 must be defective If there is an accumulation of substance C, then enzyme 3 must be defective

1941- Beadle and Tatum • Prior work done:one-gene-one enzyme hypothesis suspected but not stated • Able to show the relationship between genes and enzymes • Purpose: "to determine if and how genes control known biochemical reaction" • Work with bread mold Neurosporacrassa

Easy to grow and maintain • Easy to induce mutation • Easy to identify and isolate mutants

Complete Medium Minimum Medium Minimum Medium + Amino Acid Histidine Proline Leucine Lysine Arginine Valine Tryptophan

argF (gene) argH (gene) Precursor Citrulline arginine Enzyme B Enzyme D Enzyme A Enzyme C Ornithine Arginino-succinate argE (gene) argG (gene) If the precursor accumulated, the defect was in enzyme A If ornithine accumulated, enzyme B was defective

They showed that a lack of a particular enzyme corresponded to a mutation in a specific gene • Conclusion: a gene acts by directing the production of only one enzyme • This relationship was summarized as the one-gene-one-enzyme hypothesis

Vernon Ingram further proved the results of Beadle and Tatum while studying the amino acid sequence of hemoglobin from individuals with sickle cell anemia • Significance of Ingram’s findings: he linked a human hereditary abnormality to a single alteration in the amino acid sequence of a protein

Protein Synthesis

The central dogma of molecular biology is the proposition put forward by Francis Crick The information flow in the cell goes from the deoxynucleicacid DNA, to the ribonucleic acid messenger RNA, to protein Never from protein to nucleic acids.

Translation Transcription

Atype of molecule that consists of a long chain of nucleotide units. • Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate.

RNA is very similar to DNA, but differs in a few important structural details: • In the cell, RNA is usually single-stranded, while DNA is usually double-stranded • RNA nucleotides contain ribose while DNA contains deoxyribose • RNA has the base uracil rather than thymine that is present in DNA.

Transcription and Translation An Overview

Transcription

RNA Polymerase binds to the DNA at a specific site, near the beginning of the gene • This site is known as the promoter

Using the DNA as a template, RNA polymerase puts together the appropriate ribonucleotides • This way, it builds the mRNA transcript, a process known as elongation

Shorty after the RNA Polymerase passes the end of a gene, it recognizes a signal to stop transcribing • This constitutes termination • The mRNA transcript is then completely released from the DNA and will eventually exit the nucleus

Translation

Initiation occurs when a ribosome recognizes a specific sequence on the mRNA and binds to that site • The ribosome then moves along the mRNA three nucleotide at a time • Each set of three nucleotides codes for an amino acid

A tRNA delivers the appropriate amino acid and the polypeptide chain is elongated • Elongation continues until it reaches a “stop” signal

When the “stop” signal is reached, translation stops • At this point the ribosome falls off the mRNA and the polypeptide chain is released

There are 20 amino acids found in proteins but only four different basesin mRNA • A sequence of three nucleotides mustbe used for each amino acid • Each triplet of nucleotides is called a codon • If only one nucleotide coded for one amino acid, we would be limited to four amino acids • If two nucleotides coded for one amino acid, the possibilities would be 16 (42=16)

The use of three nucleotides resultsin 64 (43=64) • 64 different possible combinations easily code for the existing 20amino acids • Each triplet of nucleotides codes for a specific amino acid

More than one codon can code for a single amino acid, indicating a redundancy in the genetic code • Example:UUU, UUC, UCU, UCC all code for the amino acid Phenylalanine

Codon: Sequence of three bases in DNA or complementary mRNA that serves as a code for a particular amino acid • Start Codon: Specific codon (AUG) that signals to the ribosomes that the translation starts at that point • Stop Codon: Specific codons that signal the end of translation to a ribosome

Protein Synthesis