Protein Structure PDF

Protein Structure Color Index: Main text (black) Female slides (pink) Male slides (blue) Important (red) Dr’s Notes (green) Extra Info (grey) Editing file  Objectives Understan...

Protein Structure Color Index: Main text (black) Female slides (pink) Male slides (blue) Important (red) Dr’s Notes (green) Extra Info (grey) Editing file  Objectives Understand the peptide bonding between amino acids. Explain the different levels of protein structure and the forces stabilizing these structures and what happens when the protein is denatured. Define the α-helix and β-sheet as the most commonly encountered secondary structures in a protein molecule. Correlate the protein structure with function with hemoglobin as an example. Understand how the misfolding of proteins may lead to diseases like Alzheimer’s or prion disease.  What are Proteins? Made Up Of: Proteins are There are mainly 20 large, complex hundreds or thousands of smaller units called different types molecules that Amino Acids of amino acids play many that can be critical roles in which are attached to combined to make a the body. one another in long protein. chains. -The sequence of amino acids determines- Protein’s unique three- dimensional (3D) Specific Function. structure  What are Proteins? They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs. Proteins can be described according to their: Large range of functions in the Body, e.g. : 1 Antibody 5 Transport & Storage 3 Structural Component 2 Enzyme 4 Messenger  Notes 439: Disulfide (SS) bond links two residues of Primary structure Cysteine near to each other. -It is the linear sequence of amino acids -Not functional Covalent bonds in the primary structure of protein: Peptide bond Disulfide bond Theprimary How to determine the primary structure structure is sequence? the simplest and the first level of structure. Indirect -Peptide bonds are DNA sequencing very strong and Direct amino they require acids sequencing. enzymes to be broken.  Peptide Bond (amide bond) The amino acid The amino acids The amino acid with a free Each amino acid at the two ends with a free carboxylic group in a chain of a chain make amino group is is called carboxyl makes two only one called amino terminus or peptide bond. COOH-terminus peptide bonds. terminus or NH2-terminus. NOTE 438: Residue: amino acid in polypeptide chain We always read from N- terminus to C-terminus Note: Tripeptide has 2 peptide bonds -Peptide bond=Amide bond  Peptides Amino acids can be polymerized to form chains: Two amino acids dipeptide one peptide bond Three amino acids tripeptide two peptide bonds Four amino acids tetrapeptide three peptide bonds Few (2-20 amino acids) oligopeptide More (>20 amino acids) polypeptide  Secondary structure -It is regular arrangements of amino acids that are located near to each other in the linear sequence -Not functional -Excluding the conformations (3D arrangements) of its side chains. Examples of Secondary Structures β-sheet α-helix β-bend  α-helix It is a right-handed spiral, in which side chains of amino acids extended outward Hydrogen bonds Stabilize the α-helix. H-bonds form between the peptide bond carbonyl oxygen and amide hydrogen Amino acids per turn: Each turn contains 3.6 amino acids. Imino group → interferes Amino acids with the smooth helical Because of that disrupt structure. the Bulky side an α-helix (Proline has ring structure that chain disrupts the helical structure) valine or Glutamate, tryptophan isoleucine aspartate, histidine, lysine Proline Proline or arginine Branched amino They form acids at the β- ionic bonds carbon  β-sheet (Composition of a β-sheet) Two or more polypeptide chains make hydrogen bonding with each other. Also called pleated sheets because they appear as folded structures with edges. Antiparallel Parallel -The tail represents the N- terminus. β-sheet -The head represents the C-terminus. Hydrogen bonds in parallel direction is less stable than in antiparallel direction  Other secondary structure examples β-bends 1. β-bends (reverse turns): proline or Reverse the Usually found The name comes β-bends are because they often generally glycine are often include direction of a on the surface frequently connect successive composed of four charged polypeptide of the strands of antiparallel found in β- β-sheets. amino acid residues. chain. molecule residues bends. 2. Non Repetitive secondary structure: Glycine: smallest amino acid which makes it easier e.g. loop or coil conformation. to bend. Proline: bends due to the lack of hydrogen bonds  Other secondary structure examples -Supersecondary structures (motifs): A combination of secondary structural elements α α motif : β α β motif: β hairpin: β barrels: reverse turns connect two α helices a helix connects two rolls of β sheets antiparallel β sheets together β sheets  Tertiary Structure Tertiary structure: the three-dimensional (3D) structure of an entire polypeptide chain including side chain (R). Domains: the fundamental functional and 3D structural units. Polypeptide chains that have >200 amino acids have 2 or more domains. The core of a domain: is built from combinations of supersecondary structural elements (motifs) and their side chain. Domains can combine to form tertiary structure  Tertiary Structure Interactions stabilizing tertiary structure: Hydrophobic interactions: Hydrogen bonds: Ionic interactions: Disulfide: SS (Cysteine with between nonpolar amino between polar and oppositely charged Cysteine covalent acids in the interior of the hydrophilic amino side-chains groups polypeptide (most important acids. reactions bond). interaction that stabilizes the tertiary structure)  Protein Folding Primary structure Secondary structure Supersecondary Tertiary Structure Structure - Some proteins exist in quaternary structure (level of folding after tertiary) - Chaperons are folded Also known as “heat shock” by other chaperons. proteins ‫ألنه يزداد عند وجود الحرارة‬ They make sure that the folding process is done right  Quaternary Structure Some proteins contain two or more polypeptide chains that may be structurally identical or totally unrelated Each chain forms a 3D structure called subunit. According to the number of subunits: Dimeric, Trimeric, multimeric Subunits may either function independently of each other, or work cooperatively, e.g. hemoglobin Protein has 1 polypeptide chain → the protein has 3 levels of structure only (primary,secondary,tertiary). CREDITS: This presentation Slidesgo template was created by Slidesgo, and Protein Flaticon has >1 polypeptide chains → the protein has 4 levels of structure Freepik NOTEicons by Flaticon, and infographics & images by Freepik includes (primary, secondary, tertiary, quaternary). 441 : Nascent protein: the primary structure of a protein. Native protein: the mature protein that has been folded. The quaternary structure is the last complexity. Quaternary Structure 441 Illustration  Hemoglobin 1- Globular protein (round/spherical) 2- α₂ and β₂ (4 subunits) 3- Oligomer (Multisubunit protein) 4- two identical subunits are called protomers  Denaturation of Proteins - Denaturation results in the unfolding and disorganization of the protein’s secondary and tertiary structures. - Most proteins, once denatured, remain permanently disordered - Denatured proteins are often insoluble and, therefore, precipitate from the solution the protein in the egg “albumin” once we put it in “heat” it E.g will be denatured and become insoluble.  Heat Organic solvents Mechanical mixing Denaturing Agents Lons of heavy metals Detergents Strong acids or bases (e.g. lead and mercury)  Protein Misfolding Every protein must fold to achieve it’s normal conformation and function Abnormal folding of proteins leads to a number of diseases in human, e.g. Alzheimer’s and prion diseases Alzheimer’s disease Creutzfeldt-Jacob (prion) disease Prion protein is present in normal brain tissues. β amyloid protein is a misfolded In diseases brains, the same protein. protein is misfolded. It forms fibrous deposits or Therefore it forms insoluble plaques in the brain fibrous aggregates that damage brain cells. Summary  Take Home Messages - Native conformation of the protein: functional, fully folded structure. - Unique 3D structure of native conformation is determined by primary structure (amino acid sequence) - Interactions between amino acids side-chains guide the folding of the polypeptide chain to form secondary, tertiary, and sometimes quaternary structures that cooperate in stabilizing the native conformation of the protein. - Protein denaturation results in unfolding and disorganization of the protein’s structure, which aren’t accompanied by hydrolysis of peptide bonds. - Diseases can occur when an apparently normal protein assumes a conformation that is cytotoxic, as in the case of Alzheimer’s or Prion’s disease.  MCQs 1 Which of the following statements is true about the (primary ) 1° structure of proteins? The helical structure Subunit structure of Three-dimensional The sequence of amino A of the protein B the protein C structure of the protein D acids joined by a peptide bond 2 Which of the following diseases is caused by protein misfolding ? A Alzheimer's disease B Hypothyroidism C Adema D All 3 A peptide bond forms between which two functional groups in amino acids? Hydroxyl group and Amino group and Carboxyl group and Carboxyl group and A carboxyl group B phosphate group C amino group D methyl group 1- D. 2-A. 3-C  MCQs 4 Which secondary structure of a protein resembles a coiled helix? A Turn B Alpha-helix C Random coil D Beta-sheet adult human haemoglobin consists of 5 A 2 subunits (B, B) B 2 subunits (a, a) C 4 subunits (2a, 2B) D 2 subunits (a, B) 4- B. 5-C.  Biochemistry Team Saad AlDosari Leaders Nada AlMuhawwis Abdulrahman Turki Members Kadi Jood Alnasser Alanazi Alluhayyan Alqosi Faisal Salman Norah Horia Alnemri Almutairy Alrashid Alotaibi Abdulaziz Rahaf Latifah Mohammed Alotaibi Alshalawi Aldossary Alqahtani Basma Renad Fahad Albahkly Alsanad Almosa Ruba Team MED445 Aldibas