Proteins
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Proteins OMAR A. ALOMAIR Biochemistry 1 References Biochemistry (Lippincott's Illustrated Reviews Series), 6E Essentials of Cell Biology www.sparknotes.com Protein Synthesis • The DNA of every cell contain the nucleotides sequences required for protein biosynthesis • Protein synthesis goes through 2 major Steps: Transcription and Translation Protein Synthesis Transcription • Transcription starts with the splitting the DNA double helix • RNA polymerase enzyme align nucleotide to create complementary mRNA • Only one of the DNA Strands is utilized Protein Synthesis Transcription • Nucleotide base pairing of RNA cytosine pairs with RNA guanine guanine pairs with RNA cytosine thymine pairs with RNA adenine adenine pairs with RNA uracil Protein Synthesis Translation mRNA is released from the nucleus The ribosomal system receive the newly created mRN Protein is synthesized in the ribosomes Ribosomes contain 3 interactive site one for mRNAs two for tRNAs Protein Synthesis Translation When mRNA bind to the ribosome tRNA start the translation process tRNA has a special clover like shape that allow it to process the mRNA sequence The tail of tRNA binds to the ribosome The head of tRNA contain the anticodon area Protein Synthesis Translation The translation process starts when the mRNA bind to the ribosome The first codon of mRNA sit in the P site It always codes for methionine tRNA with complementary anticodon form a temporary base pair with a peptide bond Protein Synthesis Translation The ribosome begins to move across the mRNA The tRNA is replaced with a new complementary anticodon to create the second peptide binding The process continue until a stop codon enter the A site The new protein is released into the cytoplasm Protein Synthesis The Central Dogma Source: http://learn.genetics.utah.edu/ Protein Structure Overview • Proteins are group of amino acids connected to each other a peptide bonds • The 3 dimensional structure of any protein is the result of the amino acids sequence • Proteins can be organize into 4 levels: Primary Secondary Tertiary Quaternary • Many proteins share structurally similar elements such as α-helices and β-sheets The order of protein structure Primary Structure of Proteins • The Primary structure of any protein is the amino acids sequence • Numerous diseases that are genetic in nature cause the wrong amino acids to be used to synthesize the protein of interest • The abnormality of the amino acid sequence alters the protein functioning structure • The Alteration in the amino acid sequence of any protein can prevent the it from folding properly and carrying out its expected function • Sickle-cell anemia is an example of disease that cause anomalous amino acid arrangement Primary Structure of Proteins Normal vs Sickled blood cells Source: upload.wikimedia.org/wikipedia/commons/ • Sickled cell anemia is caused by abnormality in the structure of hemoglobin molecule Primary Structure of Proteins Peptide bond • Covalent bonds connect two amino acids • α - Carboxyl moiety of one amino acid is connected to the α-amino moiety of another • This binding is achieved through an amide linkage • The peptide bond provide a protection against denaturing the protein • This include resistance against: Heat Extreme pH High temperature Primary Structure of Proteins Peptide bond Alanine and Valine amino acids going through condensation reaction to create a peptide bond Primary Structure of Proteins Peptide bonds nomenclature • Each peptide bond has two ends • One end consist of the free amine, and it called the (N-terminal) • The other end is occupied by the (C-terminal), which is made of free carboxyl group • Conventionally, amino acids are named starting from the N- to the C-terminal • Amino acids suffix are changed to -yl, except for the C-terminal Primary Structure of Proteins Peptide bond polarity • Amide linkage is a stable part of the peptide bond • With pH range between 12 and 2, the amide linkage can’t be oxidized or reduced • Only the N-terminal or the C-terminal can be charged • Consequently, Only the two terminals can participate chemical interactions • The hydrogen bonding that form proteins secondary structures arise from the attraction between the two ends Primary Structure of Proteins Identifying amino acid sequence • Amino Acid Analyzer machine is used • Steps involved in analyzing amino acid sequence of a peptide: 1- Hydrolysis of peptide with a strong acid to cleave the peptide bond 2- Cation-exchange chromatography to separate amino acids according to their charge and hydrophobicity. 3- The amino acids solution is tainted with Ninhydrin solution 4- Each amino acid is tainted with different strength 5- The amino acid is identified spectrophotometrically Primary Structure of Proteins Identifying amino acid sequence • Amino Acid Analyzer is used to detect the specific amino acids involved in an known protein Secondary Structure of Proteins α-Helix Many different peptide helixes found in our body α-Helix is the most common one It is a spiral stricture where the side chains stick outward It is made stable through the hydrogen bonding between the carbonyl oxygen and the amide nitrogen • Example of alpha helix protein: keratin Secondary Structure of Proteins β-Sheet In Contrast to Alpha helix, all the parts of the peptide are connected with hydrogen bonds • Another difference is that more than one strand of peptide stands • The involved strands are either parallel or anti-parallel according to wither or not the start with the same terminals • Example of β-Sheet protein: Amyloid Tertiary and Quaternary Structure of Proteins Tertiary refer to the structure and function domain of protein, and final arrangement of the polypeptide Prime example of tertiary structure is globular protein Hydrophilic parts of the globular protein are usually setting outside the structure of the protein While the hydrophobic segments are covered inside the tertiary structure • Disulfide bonds stabilize the complex structure • Quaternary Structure is complex formation of 2 or more polypeptide moieties Misfolding of Proteins Improperly folded protein is malfunctioning protein The cell usually destroy theses misbehaving protein The cleaning process weaken as we grow older protein, and final arrangement of the polypeptide Amyloid build up causes Alzheimer disease when amyloid protein is formed in the brain Prion protein is an infectious protein that can produce transmissible spongiform encephalopathies Misfolding of Proteins Proteins Functions Antibody • Plasma cell produce a special type of proteins called antibodies • Antibodies ,also called immunoglobulin (Ig), main function is to neutralize bacteria and viruses • It has Y shape structure • The antibody recognize the antigen with the variable region at the tip of the Y structure • The Binding signal the immune system to react to the invasion • They also have many biochemical research application Proteins Functions Antibody upload.wikimedia.org/wikipedia/commons Proteins Functions Enzyme • Enzyme is large protein that facilitate and accelerate numerous chemical reaction in the cell • Enzyme must bind to its substrate to alter the rate of reaction • They are highly specific an require stringent structural requirements • Cofactors and coenzymes binds to enzyme and alter its function • Usually, Enzyme do not get consumed in the chemical reaction • They have an enormous role in medical research Proteins Functions Enzyme Proteins Functions Second messenger • Second messengers are proteins that regulate many physiological functions inside the cell • The are a response to first messenger which are extracellular molecules • The second massagers responds by initiating signaling cascade • They control the level proliferation • The initiate apoptotic response • The start the differentiation process Proteins Functions Second messenger Proteins Functions Structural component • The most abundant proteins in the body • They make up the cytoskeleton of every cell • They also allow the cell to cell intercellular communication • The connective tissue is made up mostly of structural protein • Similar to cytoskeleton, the allows the body to take shape and facilitate its locomotion Proteins Functions Structural component Proteins Functions Transport Proteins • Mostly founds on the membrane of Eukaryotic cell • Act as a pump that carry molecule and menials across the membrane • The transportation process can be either energy-independent Or energy-dependent • Energy-independent is accomplished through facilitated diffusion • While the energy-independent route is carried out by an active transport through the expenditure of ATPs Proteins Functions Transport Proteins Proteins Functions Receptors • Proteins act as receptors to countless neurotransmitter and chemical molecules • The binding of the ligand initiate different physiological functions • It is the main protein targeted in pharmacological treatment • They are classified into different classes according to their structure, function, and location inside the body • They can be also blocked to prevent the ligands from producing its effect Proteins Functions Receptors Beta agonists such as norepinephrine cause bronchodilation
