 Phospholipid bilayer  “Mosaic” of proteins The fluid-mosaic model

 Carry out a cell’s functions:  Cell division  Energy generation  Protein synthesis  Synthesis of hormones  Response to hormone signals  Structure  Motility  Recycling of cell materials  DNA replication  RNA synthesis  Transport across membrane  Transport within cell  Response to infection  etc., etc., etc…. Proteins “What is the secret of life?” I asked. “I forget,” said Sandra. “Protein,” the bartender declared. “They found out something about protein.“ “Yeah,” said Sandra, “that's it.” --Kurt Vonnegut in Cat’s Cradle

 Polymers of amino acids Proteins

 Side chain gives distinctive chemical properties Amino acids

 Protein = any of 20 amino acids arranged in any order Amino acids

 Amino acids joined by peptide bonds Protein structure

 Primary (1 ° ) structure = amino-acid sequence Protein structure methionineaspartateglycinephenylalaninevalinelysine N-Met-Asp-Gly-Phe-Val-Lys-C MDGFVK

 Primary (1 ° ) structure = amino-acid sequence Protein structure Lysozyme, 211 amino acids: MetLeuGlyLysAsnAspProMetCysLeuValLeu ValLeuLeuGlyLeuThrAlaLeuLeuGlyIleCys GlnGlyGlyThrGlyCysTyrGlySerValSerArg IleAspThrThrGlyAlaSerCysArgThrAlaLys ProGluGlyLeuSerTyrCysGlyValArgAlaSer ArgThrIleAlaGluArgAspLeuGlySerMetAsn LysTyrLysValLeuIleLysArgValGlyGluAla LeuCysIleGluProAlaValIleAlaGlyIleIle SerArgGluSerHisAlaGlyLysIleLeuLysAsn GlyTrpGlyAspArgGlyAsnGlyPheGlyLeuMet GlnValAspLysArgTyrHisLysIleGluGlyThr TrpAsnGlyGluAlaHisIleArgGlnGlyThrArg IleLeuIleAspMetValLysLysIleGlnArgLys PheProArgTrpThrArgAspGlnGlnLeuLysGly GlyIleSerAlaTyrAsnAlaGlyValGlyAsnVal ArgSerTyrGluArgMetAspIleGlyThrLeuHis AspAspTyrSerAsnAspValValAlaArgAlaGln TyrPheLysGlnHisGlyTyr

 Shape is critical to function!  Enzyme binds substrate  Antibody binds invading virus  Transport protein binds specific molecule Protein structure HIV Protease

 Folding determines 3D shape  Amino-acid sequence determines folding Protein structure Lysozyme, 211 amino acids: MetLeuGlyLysAsnAspProMetCysLeuValLeu ValLeuLeuGlyLeuThrAlaLeuLeuGlyIleCys GlnGlyGlyThrGlyCysTyrGlySerValSerArg IleAspThrThrGlyAlaSerCysArgThrAlaLys ProGluGlyLeuSerTyrCysGlyValArgAlaSer ArgThrIleAlaGluArgAspLeuGlySerMetAsn LysTyrLysValLeuIleLysArgValGlyGluAla LeuCysIleGluProAlaValIleAlaGlyIleIle SerArgGluSerHisAlaGlyLysIleLeuLysAsn GlyTrpGlyAspArgGlyAsnGlyPheGlyLeuMet GlnValAspLysArgTyrHisLysIleGluGlyThr TrpAsnGlyGluAlaHisIleArgGlnGlyThrArg IleLeuIleAspMetValLysLysIleGlnArgLys PheProArgTrpThrArgAspGlnGlnLeuLysGly GlyIleSerAlaTyrAsnAlaGlyValGlyAsnVal ArgSerTyrGluArgMetAspIleGlyThrLeuHis AspAspTyrSerAsnAspValValAlaArgAlaGln TyrPheLysGlnHisGlyTyr

 Secondary (2 ° ) structure = local folding Protein structure  -helix  -sheet

 Held together by non-covalent interactions Protein structure

 Tertiary (3 ° ) structure = overall 3D structure Protein structure

 Tertiary (3 ° ) structure = overall 3D structure Protein structure myoglobin fatty acid binding protein CheY

 Protein may fold into distinct domains Protein structure pyruvate kinase PEP + ADP → Pyruvate + ATP regulatory domain PEP binding domain ADP binding domain

 Quaternary (4 ° ) structure = intermolecular interaction Protein structure

 Quaternary (4 ° ) structure = intermolecular interaction Protein structure

 Unfolding: disruption of non-covalent interactions Denaturation

 Proteins can be denatured by heating Denaturation

 Proteins have optimum temperature and pH for activity Denaturation temperature → protein function → pH → protein function → enzyme from Listeria bacteria enzyme from human cells enzyme from hot spring bacteria pepsin yeast enzyme human hemoglobin 737

 What happens when a protein denatures, or misfolds? Denaturation

Prions: Pathogens without genes Normal form of Prion Protein is found in nerve cells but exact function is unknown. Abnormal form is folded in “sheets” rather than helices

 Loss of dopaminergic neurons of the substantia nigra in the midbrain.  Loss of motor skills Parkinson’s Disease

alpha synuclein

 Causes Parkinson’s Disease.  Can be passed from cell to cell. Alpha-Synuclein JA Steiner et al. 2011

 Trans-membrane (integral) proteins  Peripheral membrane proteins Fluid-mosaic model

Rhodopsin structure retinal trans-membrane domain (hydrophobic)

RPE65 structure