1 / 34

Lecture 1: Fundamentals of Protein Structure

This lecture covers the basics of protein structure, including the primary structure, amino acid anatomy, R-group characteristics, peptide bonds, secondary structure (alpha-helix, beta-sheet, and turns), tertiary and quaternary structures, and various classes of proteins.

selliott
Download Presentation

Lecture 1: Fundamentals of Protein Structure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lecture 1: Fundamentals of Protein Structure

  2. Frank Lloyd Wright

  3. Levels of Protein Structure

  4. Primary structure = order of amino acids in the protein chain

  5. Anatomy of an amino acid

  6. Non-polar amino acids

  7. Polar, non-charged amino acids

  8. Negatively-charged amino acids

  9. Positively-charged amino acids

  10. Charged/polar R-groups generally map to surfaces on soluble proteins

  11. Non-polar R-groups tend to be buried in the cores of soluble proteins Myoglobin Blue = non-polar R-group Red = Heme

  12. Membrane proteins have adapted to hydrophobic environments

  13. protonated unprotonated ( ) Some R-groups can be ionized The Henderson-Hasselbalch equation allows calculation of the ratio of a weak acid and its conjugate base at any pH

  14. General protein pK’ values • Approximate pK' • Group In a “Typical” Protein • -carboxyl (free) 3 (C-terminal only) • -carboxyl (Asp) 4 • -carboxyl (Glu) 4 • imidazole (His) 6 • sulfhydryl (Cys) 8 • 1˚-amino (free) 8 (N-terminal only) • -amino (Lys) 10 • hydroxyl (Tyr) 10 • 2˚-amino (Pro)(free) 9 (N-terminal only) • guanido (Arg) 12

  15. An example of a Henderson-Hasselbalch calculation • What is the structure of the histidine side chain at pH 4? 4 = 6.0 - log [HB]/[B-] -2 = -log [HB]/[B-] 2 = log [HB]/[B-] 100 = [HB]/[B-] • So, in a solution of histidine at pH 4, the majority structure is that of the protonated form.

  16. Some R-groups can modified

  17. Amino Acids Are Joined By Peptide Bonds In Peptides - a-carboxyl of one amino acid is joined to a-amino of a second amino acid (with removal of water) - only a-carboxyl and a-amino groups are used, not R-group carboxyl or amino groups

  18. Chemistry of peptide bond formation

  19. The peptide bond is planar This resonance restricts the number of conformations in proteins -- main chain rotations are restricted tof and y.

  20. small hydrophobic large hydrophobic polar positive charge negative charge DnaG E. coli ...EPNRLLVVEGYMDVVAL... DnaG S. typ ...EPQRLLVVEGYMDVVAL... DnaG B. subt ...KQERAVLFEGFADVYTA... gp4 T3 ...GGKKIVVTEGEIDMLTV... gp4 T7 ...GGKKIVVTEGEIDALTV... : : * * * : : : : Primary sequence reveals important clues about a protein • Evolution conserves amino acids that are important to protein structure and function across species. Sequence comparison of multiple “homologs” of a particular protein reveals highly conserved regions that are important for function. • Clusters of conserved residues are called “motifs” -- motifs carry out a particular function or form a particular structure that is important for the conserved protein. motif

  21. Generally only a limited amount of a protein’s surface is well conserved Invariant (the residue is always the same, e.g. Asp) Conserved (the residue is generally similar, e.g. negatively charged) Not conserved (can be many different residues in different species)

  22. Secondary structure = local folding of residues into regular patterns

  23. The a-helix • In the a-helix, the carbonyl oxygen of residue “i” forms a hydrogen bond with the amide of residue “i+4”. • Although each hydrogen bond is relatively weak in isolation, the sum of the hydrogen bonds in a helix makes it quite stable. • The propensity of a peptide for forming an a-helix also depends on its sequence.

  24. The b-sheet • In a b-sheet, carbonyl oxygens and amides form hydrogen bonds. • These secondary structures can be either antiparallel (as shown) or parallel and need not be planar (as shown) but can be twisted. • The propensity of a peptide for forming b-sheet also depends on its sequence.

  25. b turns • b-turns allow the protein backbone to make abrupt turns. • Again, the propensity of a peptide for forming b-turns depends on its sequence.

  26. Which residues are common for a-helix, b-sheet, and b-turn elements?

  27. Ramachandran plot -- showsf and yangles for secondary structures

  28. Tertiary structure = global folding of a protein chain

  29. Tertiary structures are quite varied

  30. Quaternary structure = Higher-order assembly of proteins

  31. Example of tertiary and quaternary structure - PriB homodimer Example is PriB replication protein solved at UW: Lopper, Holton, and Keck (2004) Structure12, 1967-75.

  32. Example of quaternary structure - Sir1/Orc1 heterodimer Example is Sir1/Orc1 complex solved at UW: Hou, Bernstein, Fox, and Keck (2005) Proc. Natl. Acad. Sci.102, 8489-94.

  33. Examples of other quaternary structures TetramerHexamerFilament SSBDNA helicaseRecombinase Allows coordinated Allows coordinated DNA binding Allows complete DNA binding and ATP hydrolysis coverage of an extended molecule

  34. Classes of proteins Functional definition: Enzymes: Accelerate biochemical reactions Structural: Form biological structures Transport: Carry biochemically important substances Defense: Protect the body from foreign invaders Structural definition: Globular: Complex folds, irregularly shaped tertiary structures Fibrous: Extended, simple folds -- generally structural proteins Cellular localization definition: Membrane: In direct physical contact with a membrane; generally water insoluble. Soluble: Water soluble; can be anywhere in the cell.

More Related