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

2.  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

3.  Polymers of amino acids Proteins

4.  Side chain gives distinctive chemical properties Amino acids

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

6.  Amino acids joined by peptide bonds Protein structure

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

8.  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

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

10.  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

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

12.  Held together by non-covalent interactions Protein structure

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

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

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

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

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

19.  Unfolding: disruption of non-covalent interactions Denaturation

20.  Proteins can be denatured by heating Denaturation

21.  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

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

23. 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

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

25. alpha synuclein

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

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

28. Rhodopsin structure retinal trans-membrane domain (hydrophobic)

29. RPE65 structure