Structure-Function Relationship in Specific Proteins PDF

STRUCTURE-FUNCTION RELATIONSHIP IN SPECIFIC PROTEINS Lesson 4 Structure-function relationship in specific proteins • Globular proteins: Hemoglobin and Myoglobin • Fibrous proteins: 1. Collagen Myosin 3. Actin fibers 2. Globular proteins CHARACTERISTICS: • Compact shape • Globular estructure...

STRUCTURE-FUNCTION RELATIONSHIP IN SPECIFIC PROTEINS Lesson 4 Structure-function relationship in specific proteins • Globular proteins: Hemoglobin and Myoglobin • Fibrous proteins: 1. Collagen Myosin 3. Actin fibers 2. Globular proteins CHARACTERISTICS: • Compact shape • Globular estructure (rounded) • Water soluble  Can be dissolved in blood • Variety of biological functions: enzymes, transport proteins, motor proteins, regulatory proteins, immunoglobulins… Globular proteins: Soluble proteins with a globular (somewhat rounded) shape. Globular proteins • Myoglobin and Hemoglobin Conjugated proteins  Heme proteins 1. Apoprotein aa 2. Prosthetic group Heme group Myoglobin Hemoglobin • Muscle • Stores oxygen • Localized oxygen reserves for times of intense respiration • Tertiary structure • • • • Erythrocytes Oxygen transport from the lung to the tissues CO2 transport from tissues to lungs (waste) Quaternary structure Globular proteins Myoglobin and Hemoglobin Prosthetic group Heme group Complex organic ring structure  Protoporphyrin Iron atom in its ferrous (Fe2+) state The iron atom of heme has 6 coordination bonds: • 4 in the plane of, and bonded to, the flat porphyrin ring system • 2 perpendicular to it Proximal His O2 Globular proteins • The heme is positioned within a hydrophobic pocket of the apoprotein : 1. 2. • Myoglobin To protect iron from oxidation. To avoid CO from binding the heme group. Important (and conservated) aa residues in myoglobin and hemoglobin 1. 2. Proximal His  coordinated with iron (perpendicularly) Distal His close to the Fe but not bound to it and favours the entry of Oxygen instead of other compounds like CO Globular proteins Hemoglobin • Transports gases through the blood • Oligomeric protein  Quaternary structure Contains 4 polypeptide chains and 4 heme prosthetic groups 2 α subunits 2 β subunits The subunits are arranged in symmetric pairs Noncovalent interactions between its subunits Globular proteins • 4 O2 binding sites • 2 Conformations of the subunits: Hemoglobin Allosteric protein: A protein (generally with multiple subunits) with multiple ligand-binding sites, such that ligand binding at one site affects ligand binding at another.  T state  Tense Without oxygen  R state  Relaxed  Oxygen binded • The binding of O2 to a Hb subunit in the T state triggers a change in conformation to the R state Oxygen binding to hemoglobin is both allosteric and cooperative T → R transition The binding of the first oxygen facilitates the binding of oxygen to the other subunits. Globular proteins Hemoglobin AGENTS THAT AFFECT OXYGEN BINDING • Protons and CO2  End products of cellular respiration from tissues (waste)  High protons and CO2 concentration of peripheral tissues reduced the affinity of Hb for oxygen ConsequentlyO2 is released to the tissues. CO2 binds to hemoglobin • 2,3-bisphosphoglycerate (BPG)  Physiological adaptation to high altitudes  Decrease in the affinity of Hb for oxygen ConsequentlyO2 is less readily bound to hemoglobin, but easier to release in the tissues Fibrous proteins • Insoluble in water  high concentration of hydrophobic amino acid residues both in the interior of the protein and on its surface • Adapted for structural functions  strength and/or flexibility to the structures • Elaborate supramolecular complexes  similar polypeptide chains are packed together Collagen Myosin Actin fibers Fibrous proteins • Structural functions  Strength • Connective tissue  tendons, cartilage, matrix of bone and the cornea of the eye • The most abundant protein in mammals Collagen Fibrous proteins COLLAGEN HELIX • Secondary structure  left-handed helix • Three amino acid residues per turn • Aa sequence Gly–X–Y, X often Pro Y  often 4-HPro 1/3 Gly, 20% Pro and OH-Pro, Ala, OH-Lys. TROPOCOLLAGEN • 3 collagen helix are twisted about each other • Right-handed  Strength COLLAGEN FIBERS • Tropocollagen is associated in a variety of ways to provide different degrees of tensile strength Collagen Fibrous proteins Collagen COLLAGEN FIBERS • Tropocollagen is associated in a variety of ways to provide different degrees of tensile strength • Covalent bonds  Cross-linked • Different collagen fibers have different number of crosslinks. • Depending on the number of cross-links collagen fibers are more rigid or flexible. • Cross-links increase in number with age. Fibrous proteins Collagen COLLAGEN TYPES • At least 27 types  depending on cross-links present  Function TYPE TISSUE DISTRIBUTION CHARASTERISTICS MAIN FUNCTION I Skin, bone, tendon, teeth Thick, closely packed, strong. Lots of cross links Resistance to tension II Elastic cartilages Very thin fibres Resistance to intermittent pressure III Smooth muscle, uterus, arteries, liver, spleen, lung, kidney Loosely packed thin fibres Structural maintenance in expansible organs IV Epithelial and endothelial basal laminae NO fibres Support and filtration Fibrous proteins Collagen DISEASES ASSOCIATED WITH GENETIC OR METABOLIC DISORDERS OF COLLAGEN Osteogenesis imperfecta Scurvy  Genetic disorder  fragile bones that  Caused by lack of  Commond name   Helix is not stable breaks easily brittle bone disease Vitamin C  Required to form hydroxyproline  Mutation in collagen helix  shorter  General degeneration of connective tissue  Affects collagen type I  Symptoms  small hemorrhages, tooth loss, poor wound healing, bone pain and degeneration, heart failure….  Vit C  Fruits and vegetables Fibrous proteins Myosin • Six subunits 2 heavy chains 2 light chains • Carboxyl terminus  extended α hélix  Left handed supercolid hélix • Amino terminus  large globular domain containing a site where ATP is hydrolyzed • The light chains are associated with the globular domains Fibrous proteins Myosin THICK FILAMENTS • Agreggation of hundred myosin molecules • Muscle cells  core of the contractile unit • Bipolar structure Fibrous proteins Actin • G-actin (globular actin)  Monomeric actin • F-actin (filamentous actin)  assemblage of G-actin monomers that polymerize two by two. Right-handed. THIN FILAMENT • F-actin + troponin + tropomyosin • Muscle cells  Each actin monomer in the thin filament can bind tightly and specifically to one myosin head group Fibrous proteins Fibrous proteins