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The structural organization within proteins Kevin Slep June 13 th , 2012

The structural organization within proteins Kevin Slep June 13 th , 2012. From Linear Peptide to a 3D Fold 1951. Herman Branson . Robert Corey. Linus Pauling. The Amino Acid The Building Blocks of Proteins. The 20 Amino Acids The Building Blocks of Proteins.

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The structural organization within proteins Kevin Slep June 13 th , 2012

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  1. The structural organization within proteinsKevin SlepJune 13th, 2012

  2. From Linear Peptide to a 3D Fold1951 Herman Branson Robert Corey Linus Pauling

  3. The Amino AcidThe Building Blocks of Proteins

  4. The 20 Amino AcidsThe Building Blocks of Proteins

  5. The Peptide Chain, Primary StructureAssembled by the Ribosome During Translation

  6. Peptide Backbone: Phi Psi AnglesLimits to their distribution

  7. Ramachandran PlotEnergy limits to the Phi Psi Distribution

  8. Soluble Proteins: E The Globular Protein FoldExterior: HydrophillicInterior: Hydrophobic H D P L I F S V R A Y C M W N T G K Q Packing Cross Section of a Globular Protein How would the organization of a Membrane Protein compare?

  9. Interactions That Stabilize Protein Folds

  10. Secondary StructureHelicesStrandsand Loops

  11. Solution NMR Nuclear Magnetic Resonance Distance Constraints Dynamic Snapshot X-ray Crystallography Electron Density Static Snapshot First: How do we determine structure? Our Tools:

  12. Secondary Structure: The a-Helix 3.6 residues per turn

  13. Secondary Structure: The a-Helix Helical Axis

  14. Secondary Structure: The a-HelixHelical Wheel – Hydropathy Plots Helical Axis

  15. Forms of Helices

  16. Secondary Structure:The b-Sheet: Parallel b-Strands

  17. Secondary Structure:The b-Sheet: Parallel b-Strands

  18. Secondary Structure:The b-Sheet: Anti-Parallel b-Strands

  19. Secondary Structure: LoopsLinkers, Variable Structrure, Active Site

  20. Cystine: The Disulfide BondTwo Cysteines Covalently Bond (Oxidation)Provides Added Stabilization to a Fold

  21. Secondary Structure Prediction ToolsOnline Sites:Predict Protein http://www.predictprotein.org/ Phyre http://www.sbg.bio.ic.ac.uk/phyre/ Jpred3 http://www.compbio.dundee.ac.uk/~www-jpred/

  22. Secondary Structure:

  23. Structure is Conferred by Main Chain Conformation and Side Chain Conformation – PackingRotamers: Favored Geometries/Energy States Phenylalanine

  24. How Secondary Structure is Organized:Motifs and Tertiary Structure

  25. Topology DiagramsJane Richardson (Duke Univ.) Triose Phosphate Isomerase

  26. Structural Motifsb Hairpin

  27. Structural MotifsHelix-Loop-Helix

  28. Structural MotifsEF-Hand Calmodulin: 4 EF Hands

  29. Structural MotifsZinc_Finger Two Histidines on a Helix Two Cysteines on a Loop

  30. Structural MotifsGreek Key

  31. Structural MotifsGreek Key Pre-albumin

  32. Structural MotifsJelly Roll

  33. Structural Motifsb-a-b

  34. Structural MotifsRossmann Fold Nucleotide Binding

  35. Helix-Turn-HelixDNA Binding Proteins

  36. Four-Helix Bundle

  37. Catalytic Triad Aspartate, Histidine, Serine

  38. TIM Barrel Domain

  39. b-Barrel

  40. b-Propeller Domain Neuraminidase

  41. Non-Protein Molecules That Play a Role in Structure and Function Cofactors The Heme Group in Hemoglobin

  42. Non-Protein Molecules That Play a Role in Structure and Function Ordered Water Water in Prealbumin First Hydration Shell

  43. Non-Protein Molecules That Play a Role in Structure and FunctionIons Water in Prealbumin

  44. How Do Proteins Fold?Moving from a linear peptideTo a MotifTo a Domain

  45. Protein Folding: Energy Landscape

  46. Protein Folding: Pathways

  47. Protein Folding: Help From Chaperones

  48. Protein DomainsBuilt from Motifs

  49. a Domainsa solenoid – a curved structure peridinin-chlorophyll-containing protein - trimer

  50. b Domains WD40 protein

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