Lecture 5 sols-2019-protein struc 2
- 1. Science of Living System (BS20001) • SOUMYA DE • Office: 2nd Floor, Sir JC Bose Laboratory Complex • Phone: 03222-260514 • E-mail: somde@iitkgp.ac.in • Research interests: Biophysics Nuclear Magnetic Resonance (NMR) Spectroscopy Protein Engineering Signal Transduction and Gene Expression Enzymology
- 3. Protein Molecules are Organized in a Structural Hierarchy Secondary Tertiary Primary Quaternary
- 4. Secondary Protein Structure Beta Sheet Alpha helix Characterized by main chain NH and CO groups participating in H-bonds
- 5. Alpha Helix Every 3.6 residues make one turn The distance (pitch of helix) between two turns is 5.4 Å The C=O of residue ‘n’ is hydrogen bonded to N-H of residue ‘n+4’ n n+1 n+2 n+3 n+4 n+5
- 6. The Alpha-Helix has a Dipole Moment n n+1 n+2 n+3 n+4 n+5 The dipoles of peptide units are aligned along the α helical axis
- 7. Less Preferred: Pro, Gly, Tyr, Ser Some Amino Acids are Preferred in α-Helices Good helix formers: Ala , Glu, Leu , Met
- 8. Alpha helix can be – Right- handed or Left handed BUT, left handed helix is not possible for L-amino acids due to close approach of the side chains and CO group. Right handed – most commonly observed in proteins. Alpha Helix: Right-handed or Left-handed?
- 10. Helical Wheel: Each residue can be plotted every 360/3.6=100° around a circle or spiral Hydrophobic Hydrophilic Charged Totally buried Partially buried Exposed
- 11. β-sheet (Number of β-Strands are Involved) β-sheet from several regions of the chain; Each β-strand, typically 5-10 residues long α-helix: from one continuous region H-bonds are perpendicular to strands
- 12. β-pleated sheet: ‘pleated’ because side chains point up and down alternatively Parallel and Antiparallel β-sheet
- 13. Mixed β-sheet
- 14. Loop regions mostly occur at the surface of protein molecules
- 15. Hair Keratin
- 16. Hair Keratin
- 17. Chemistry of Straight and Curl Hair
- 18. Polypeptide Chains Fold into Several Domains •Fundamental unit of tertiary structure – DOMAIN •Domain: polypeptide chain or a part of polypeptide chain that can independently fold into a stable tertiary structure •Domains are also units of function Tertiary structure refers to the spatial arrangement of amino acid residues that are far apart in the sequence and to the pattern of disulfide bonds.
- 19. Quaternary Structure Proteins containing more than one polypeptide chain exhibit a fourth level of structural organization. Each polypeptide chain in such a protein is called a subunit. Quaternary structure refers to the spatial arrangement of subunits and the nature of their interactions. The simplest quaternary structure is a dimer, consisting of two identical subunits.
- 20. Quaternary Structure (higher order) Complex Quaternary Structure. The coat of rhinovirus comprises 60 copies of each subunits The α2β2 tetramer of human haemoglobin. The structure of the two identical α subunits (red) is similar to but not identical with that of the two β subunits (yellow).
- 21. • Structure Function • Structure Mechanism • Structure Origins/Evolution • Structure-based Drug Design • Solving the Protein Folding Problem Solving Protein Structures Only 2 kinds of techniques allow one to get atomic resolution pictures of macromolecules QHTAWCLTSEQHTAAVIWDCETPGKQNGAYQEDCA HHHHHHCCEEEEEEEEEEECCHHHHHHHCCCCCCC H: α-helix E: β-strand C: unstructured
- 22. Methods to study protein structures X-ray crystallography NMR spectroscopy • Prof. Amit K Das (http://www.iitkgp.ac.in/department/BT/faculty/bt-amitk) • Prof. Dibyendu Samanta (http://iitkgp.ac.in/department/BS/faculty/bs-dibyendu.samanta) • Nuclear magnetic resonance (NMR) spectroscopy • Prof. Soumya De (http://iitkgp.ac.in/department/BS/faculty/bs-somde) Structure-guided protein engineering
- 23. Hemoglobin A: Val-His-Leu-Thr-Pro-Glu-Glu-Lys- Hemoglobin S: Val-His-Leu-Thr-Pro-Val-Glu-Lys- “sticky patch” causes hemoglobin S to agglutinate (stick together) and form fibers which deform the red blood cell Importance of Protein Structure