1 / 45

Protein structural element

Protein structural element. Yun-Ru (Ruby) Chen 陳韻如 Ph.D. The Genomics Research Center (office at 7th floor) yrchen@gate.sinica.edu.tw 2789-9930 ext 355. outline. Atom interaction and bonding Amino acid and peptide bond Secondary structure Tertiary structure Quantiary structure

joy-reed
Télécharger la présentation

Protein structural element

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. Protein structural element Yun-Ru (Ruby) Chen 陳韻如 Ph.D. The Genomics Research Center (office at 7th floor) yrchen@gate.sinica.edu.tw 2789-9930 ext 355

  2. outline • Atom interaction and bonding • Amino acid and peptide bond • Secondary structure • Tertiary structure • Quantiary structure • Function

  3. Bonding

  4. Atom Interactions Energy Covalent interaction 300-400x Non-covalent interaction noncovalent interactions are 10-100 times weaker than covalent bonds.

  5. Non-covalent interactions

  6. Charge-charge interaction Coulomb's law defines the force between a pair of charges (q1 and q2) separated by a vacuum by a distance, r as F = k*(q1q2)/r2, where k is a constant. DE in vacuum=120kcal/M (very strong) In non-vacuum, dielectric medium F = k*(q1q2)/(D*r2) The dielectric constant arises from the fact that the dielectric medium shields the charges from each other. D water=79 dE in solution is lower because of hydration

  7. Hydrogen bond • Hydrogen is shared between 2 electronegative atoms • Directional • Stronger than van der waal • Strength depends on donor and Acceptor electronegativity • (O>N>S)

  8. Van der Waal Van der Waal radius of atoms

  9. Peptide bond Carboxyl group(-COOH)=~2 Amide (-NH3+)=~9.6 Charged residues Acidic: Asp, D, pK1=~3.9, b-carboxyl. Glu, E, pKa=~4.3, g-carboxyl Basic: Lys, K, pK1=~10.5, b-carboxyl. Arg, R, pKa=~12.5, g-carboxyl His, H, pKa=~6, Hydroxyl residues Ser, pKa=~13.6 Thr, pKa=~13.6 Cys,pKa=~10.3 Protonation pKa<pH, deportonated pKa=pH, half-half pKa>pH, protonated pKa

  10. Histidine

  11. Hydroxyl residues • Aliphatic • pKa=13.6

  12. cis-trans Isomerization (trans:cis) • Non-proyl (1000:1) • X-proyl bond (4:1)

  13. Disulfide bonds • Cysteine v.s. Cystine • Reducing agent DTT(dithiothreitol) TCEP (Tris[2-carboxyethyl] phosphine) Glutathione (reduced form vs. oxidized form (GSSG)) g-Glu-Cys-Gly

  14. Aromatic residues

  15. labeling • Amine-reacting group Reaction of a primary amine with an isothiocyanate Reaction of a primary amine with a succinimidyl ester or a tetrafluorophenyl (TFP) ester

  16. Reaction of a primary amine with an STP ester Reaction of a primary amine with a sulfonyl chloride

  17. Thiol group Reaction of a thiol with an alkyl halide Reaction of a thiol with a maleimide Reaction of a thiol with a symmetric disulfide (e.g., didansyl-L-cystine, D146).

  18. Steric constrains dictate the possible types of secondary structure Ramachandran plot psi phi

  19. Protein secondary structure Turn: beta turn, reverse turn, hairpin turn The simplest secondary structure element 3 or 4 aa involved

  20. Helix • Alpha-helices are versatile cylindrical structures stabilized by a network of backbone hydrogen bonds • Helices can be right-handed (favored) or left-handed • 3.6aa per turn (a rotation of 100A) • 7aa for a helical wheel

  21. Helical (macro)dipole (N-ter: positive; C-ter: negative)

  22. Helical wheel Alpha-helices can be amphipathic with one polar and one non-polar face (favored helix-helix interaction) Lucine zipper

  23. Special cases Collagen triple helix: proline found in left handed helices, three helices coil around each other Polyproline: when the peptide bonds are all trans it forms a left-handed helix with three residues per turn. Often serve as a docking sites for protein recognition modules such as SH3 domains in signal transduction pathways (exist in unfolded protein)

  24. Beta sheets are extended structures that sometimes form barrels

  25. Parallel strand must be joined by long connections

  26. Certain aa are more usually found in alpha helices, others in beta sheets • Long side chains are often found in helices • Side chain branched at b-carbon are often found in b stand • Proline and glycine are disfavored in helix and sheet • Predication is based on empirical rules (Chou-Fasman) • None is completely accurate

  27. Condensed multiple secondary elements leads to tertiary structure (all alpha, all beta, mixed alpha/beta) V domain of IG light chain Triosephosphate isomerase Dihydrofolate reductase

  28. Bound water In unfolded protein: backbond contacts with water In folded protein: water release from backbond contacts to bulk water, but water still interact with polar group on the surface either peptide bond and side-chains.

  29. Hydrophobic effect • The tendency of nonpolar groups in water to self-associated and thereby minimize their contact surface are with the polar solvent • Exclusion of water • A driving force for folding

  30. solubility

  31. Proteins are flexible molecules

  32. Quaternary structure

  33. Protein interacting domains

  34. Reading Assignment • Chapter1 of Protein Structure and Function (or any other protein structure text book)

More Related