Proteins

Proteins

1. Functional Classification

   • Structural proteins
     • Collagen
       • Fibrous Protein
         • Tropocollagen molecules
           • arranged head to tail
           • 40nm gap between molecules
             • accommodates lysyl oxidase
       • Amino acids
         • Glycine, Proline, Hydroxyproline repeat
         • Proline prevents the formation of alpha helices
         • Regular glycine achieves compact packing
       • Helical Structure
         • initial LH helix
           • 3 aggregate to form triple helix
             • RH twist
       • synthesised as procollagen
         • Pro sequence at C and N terminals
           • no helical arrangement due to lack of glycines
           • high cysteine content: high disulfide bonding
         • cleaved to form tropocollagen
         • secreted by fibroblast cells
       • collagen disorders
         • Osteogenesis Imperfecta
           • brittle bones and bone deformaties
           • glycine replacement by cysteine or arginine
           • no fibre formation
         • Scurvy
           • Lack of vitamin C (ascorbic acid)
           • reduced hydorxylation of proline
             • Less stable triple helix
           • fragile capillaries, poor healing
         • Ehlers- Danlos
           • Collagen 2 defect
           • weakened connective tissue
             • dislocations
             • hyperextensible skin
           • deficient cross linking
     • Histones
       • Packaging of DNA
         • Octomeric unit of histones forms nucleosome core
         • H1 associate to form solenoids
       • 5 types of histones
         • H1
         • H2a
         • H2b
         • H3
         • H4
       • Rich in lysine
       • +ve charge to facilitate DNA
   • Regulatory
     • control activity of other proteins
     • .e.g. steroid receptor
       • Mutation in eclampsia (high BP in pregnancy)
         • aa substitution: ser -> leu
         • increased affinity for progesterone
         • inc. Na+ uptake in kidney
       • lipid hormones freely diffuse: receptor inside cell
       • interacts with DNA to change transcription
       • functional domains
         • carboxyl domain
           • binding site
           • dimerizing region
         • amino terminal
           • interacts with transcription machinary
         • central region
           • interacts with DNA hormone binding site
             • aa region recognised is alpha-helical structure
               • anchored by cysteine iron complex
   • Catalytic
     • enzyme functions to increase rate of reaction
     • .e.g Hexokinase
       • Catalyses the reaction to glucose to glucose-6-P
         • self regulated G-6-P inhibits enzyme
       • Isoforms in muscle and liver
       • 2 domain structure
         • Glucose: substrate
         • ATP: regulator
   • Translocatory/Transport
     • movvement of molecules across permeability barriers
     • amphipatic properties
     • .e.g ATP binding cassette
       • multidrugs efflux pump
       • two domains: transmembrane and nucleotide binding
       • powered by hydrolysis of ATP
         • causes a conformational change
       • multiple roles
         • uptake of sugars, aa and metal ions
         • export of toxins and drugs
         • TAP1/2 peptide exporter
         • uptake of fatty acids in peroxisimes
           • defective in adrenoleukodystrophy
         • Chloride efflux channel CFTR
         • multidrug resistance
           • cancer

2. Proteins are specific to different locations

   • ECM: collagen, proteoglycan and elastin
   • Plasma membrane: transporters and receptor
   • Blood: albumins, globulins, fibrinogen, RBC
   • Cytoskeleton: actin, tubulin, spectrin
   • Mitochondria: F1F0- ATP synthase
   • nucleus: histones, polymerases