Protein Classification and Function PDF

Protein Classification and Function Caner GEYİK, PhD [email protected] 2024  2 Learning Objectives After this activity, students can ; Classify proteins Explain struc...

Protein Classification and Function Caner GEYİK, PhD [email protected] 2024  2 Learning Objectives After this activity, students can ; Classify proteins Explain structural properties of fibrous proteins Explain structural differences among keratin, collagen, and elastin Define globular proteins and their structural properties Explain the structure and function of myoglobin and its oxygen saturation Explain the structure and function of hemoglobin and its oxygen saturation 3  4 Classification of Proteins Shape of the protein which is determined by Structural sequence. Molecules other than amino acids can be part of Composition proteins. Enzymes, receptors, carriers, storage, defence, Function etc.  5 Classification of Proteins Structural (Shape) Fibrous Globular Supports cell Regulation shape Catalytic activity Protective roles Transport Mechanical properties  6 Classification of Proteins Structural (Shape) Fibrous Globular  7 Classification of Proteins Composition Simple Conjugated Only amino acids Metals (metalloproteins), lipids Another name: (lipoproteins), carbohydrates homoproteins (glycoproteins), etc. (Prosthetic groups) Protein part: apoprotein Another name: heteroproteins  8 Classification of Proteins Composition Simple Conjugated  9 Fibrous Proteins Scleroproteins Not soluble in water Can’t be digested Thermostable Have mechanical strength  10 Fibrous Proteins Keratin (Ectodermal) Collagen (Mesenchymal) Elastin (Mesenchymal) Silk Fibroin Muscle Proteins Tropomyosin (Thin muscle fibre) Myosin (tail) (Thick muscle fibre)  11 Keratin  12 Keratin The cysteine content in the hair structure is around 14%. reduction curling oxidation As the cysteine ratio increases, the hardness of keratin increases (nails, horns) Disulfide bonds gives insolubility property Cysteine is low in skin keratin.  13 Keratin - Perm Thioglycolic acid, HSCH2COOH Hydroge Peroxide, H2O2  14 Collagen It constitutes ~30% of total protein and 6% of body weight. There are 28 types of collagen in the human body. Rich for Proline (Pro) and Hydroxyproline (Hyp) Physical properties changes depending on the tissue it is found: Skin, veins : Elasticity Bones, teeth: Hardness Tendons, ligaments: Pulling power  15 Fe2+ Fe2+  16 Collagen  17 Collagen Covalent cross links stabilise the structure Lysil oxidase condensation Aldeyhyde species -amino group of lysine is seperated and remanining -C is oxidised to aldehyde  18 Clinical Relevance of Collagen Disease Reason Symptom / Clinical Table Scorbutus Hydroxyproline deficiency, failure Delayed wound healing, Capillary to form Tropocollagen cross- bonds fragility increased Ehlers-Danlos Type III Collagen defect (Gene Dislocated joints, Musculoskeletal Syndromes anomally) deformities, Skin anomalies, Artery and uterine ruptures Osteogenesis Type I Collagen synthesis deficiency Bone deformities and breaks imperfecta  19 Elastin Durability and flexibility of the skin, blood vessels and lungs. It is a hydrophobic protein, 800 amino acids long. It is rich in glycine, alanine and lysine, but poor in proline. It contains small amounts of hydroxyproline. It does not contain any hydroxylysine.  20 Cross-links in Elastin Desmosine Lysine-Norleucine H H O O H H  N C C C C N (CH2)2 (CH2)2 CH2  CH2 H N C N H     C CH2 C C CH2 CH2 C H CH2 H CH2   NH O C C C C O + CH2 N CH2 CH2 (CH2)2 (CH2)3  C C N C C N O H H O H H  21 Differences Between Collagen and Elastin Collagen Elastine Different genetic types Single genetic type Random coils for elasticity Triple helix No structured repeats (Gly-X-Y)n repeats Hydroxylysine is absent Hydroxylysine is present Carbohydrate modification is Carbohydrate modification is absent present Desmosin and Lysine-Norleucine Aldol cross-links cross-links Elongated peptides (tails) during No added parts during biosynthesis biosynthesis  22 Silk Fibroin  23 Silk Fibroin  β-pleated sheet  Nearly half of the amino acids are Glycine  R groups of alanine ve serine place opposite of R group of glycine Most elongated form of β-pleated sheet structure Many weak bonds gives stability (Hydrogen and van deer Waals)  24 General Properties of Globular Proteins High solubility Mostly conjugated proteins (bound with different molecule than amino acids, «prosthetic groups») Nucleoproteins, Metalloproteins, Glycoproteins, Flavoproteins, etc. Diverse functions Catalysis, Transport, Storage, Gene regulation, Immunity, etc.  25 Albumins Albumin protein family Human Serum Albumin (most common in blood) Nearly %50 of all plasma proteins Carries ions, xenobiotics, hormones, fatty acids, …  26 Globulins Bigger than albumins Less Soluble in water 3 Classes according to their sizes Alpha globulins Beta globulins Gamma globulins Immuno globulins: Antibodies  27 Globin (Globulin subclass that contains heme group) A ferrous iron (Fe2+)atom connected to porphyrin ring from nitrogens O2 binding properties Heme (Haem, UK) αἷμα (Greek: blood)  28 Myoglobin and Hemoglobin  29 Myoglobin Myoglobin (Mr 16,700; abbreviated Mb) is a single polypeptide with one molecule of heme Can bind O2 even in low concentrations Stores O2 in muscles  30 Hemoglobin  4 polypeptide chains form a quarterny structure (2 α-like and 2 β-like subunits)  Subunits are similar to myglobin  4 heme groups can bind 4 O2 molecule  31 Hemoglobin Each chain is folded to keep the heme away from water. In the inner part of the molecule, hydrophobic amino acids surround the heme, keeping water away so that oxygen can bind reversibly, and also prevent the iron atom from oxidizing, allowing oxygen to be delivered to the tissues. This region of the polypeptide chain is called the heme pocket.  32 Hemoglobin Types 2 α-like and 2 β-like subunits α-like subunits Hb Gower 1(ζ2ε2): Embryonic yolk sac ζ ε ζ α ε ζ β-like subunits HbF (α2γ2): Fetal hemoglobin α γ ε γ δ β Stronger O2 binding γ α α β HbA (α2β2): Main adult hemoglobin β α α δ HbA2 (α2δ2): Minor adult hemoglobin δ α  33 Hemoglobin Types Glycosylation ratio is dependent on the plasma concentration of the glucose  34 Hemoglobin Binds and releases oxygen depending on the pO2 When O2 is released: Can bind CO2 (Carbaminohemoglobin) Can bind hydrogen (Deoxyhemoglobin)  35 DeoxyHb OxyHb  T State: Tight,Tense, Taut form. Affinity to O2 is low  R State: Relaxed form. Affinity to O2 is high 36  37 Bohr Effect Kanda artan karbondioksit konsantrasyonundan kaynaklanan kan pH'ının azalmasına yanıt olarak solunum pigmentinin (örneğin hemoglobin) oksijen afinitesinin azalması  38 Plasma CO2 CO2 + H2O Carbonic anhydrase Tissue H2CO3 + Hb(O2)4 O2 4O2 + H+Hb + HCO3- Bohr effect Cl- Cloride shift H+ binds to histidins in pKa 6.0 Hemoglobin  39 Alveol Plasma 4O2 + H+Hb + HCO3- HCO3- O2 Carbonic anyhdrase Hb(O2)4 + H2CO3 CO2 %85 CO2 + H2O  40 HbO2 dissosication curve shifts to right in lower pHs  41 2,3- BPG binding to Hemoglobin 2,3-Bisphosphoglyceric acid Side product of glycolysis Binds to hemoglobin and decreases the affinity for O2 Helps releasing O2 in tissues  42 2,3- BPG in Transfused Blood Without 2,3-BPG oxygen can’t be released to tissues Transfused blood may lost its 2,3-BPG molecules because of degradation. Before transfusion, blood is mixed with another solution containing 2,3-BPG molecules This solution also regenerates the degraded ATP molecules  43 2,3- BPG binding to Hemoglobin  44 Carbonmonoxide Environmental toxicants, smoking. Carbonmonoxide can bind tightly to iron in the heme group This binding is reversible but; Occupies the place where oxygen binds Increases other hemes' interest in oxygen (they do not want to release oxygen) Hyperbaric oxygen treatment