Protein Beta-Sheets Predicted in 1951 by Pauling et Al. using standard bond length and valence angles of H-bonds from small inorganic molecules. L. Pauling, R. B. Corey, The pleated sheet, a new layer configuration of polypeptide chains, PNAS (USA) 37 (1951) 251-256. Protein Beta-Sheets P A Protein Beta-Sheets Beta-Bulge Beta-Helix PDB code 1QCX Beta-Propeller PDB code 1HXN Beta-Sandwich PDB code 2RHE Beta-Barrel Beta-Barrel (1TIM) Beta-Barrel PDB code 1TIM Beta-Sheet Aggregation ªThe fact that natural beta-sheet proteins are usually soluble but that fragments or designs of beta structure usually aggregate suggests that natural beta proteins must somehow be designed to avoid this problem. Regular beta-sheet edges are dangerous, because they are already in the right conformation to interact with any other beta strand they encounter.º -> beta-sheet amyloid fibers... Richardson J.S., Richardson D.C., (2002) Natural beta-sheet proteins use negative design to avoid edge-to-edge aggregation, PNAS, 99, 2754-2759. Beta-Sheet Aggregation Beta-sheet amyloid fibers formation is associated with these neuro-degenerative deseases: - Alzheimer (AB peptide) - Senile Systemic Amyloidosis (transthyretin protein) - Spongiform Encephalopathies (ªmad cowº) (prion protein) Beta-Sheet Aggregation Various strategies employed by beta-sheet to avoid aggregation: Beta-Barrels: - no edge strand! Parallel Beta-Helix: - ends are protected by loops. Beta-Propellers and Single Sheets: - beta-bulge. - proline residue. - charged residue (that would be buried if dimerized). - short edge strand. - loop coverage. Beta-Sandwich: - charged residue. Forces Atom Charge ------------------ N -0.41 Ca -0.02 C +0.59 Hn +0.27 O -0.57 Ha +0.07 Forces C=O...C=O dipole: P. H. Maccallum, R. Poet, E. J. Milner-White, Coulombic interactions between partially charged main-chain atoms not hydrogen-bonded to each other influence the conformations of alpha-helices and antiparallel beta-sheet. A new method for analysing the forces between hydrogen bonding groups in proteins includes all the Coulombic interactions, JMB 248 (1995) 361-373. P. H. Maccallum, R. Poet, E. J. Milner-White, Coulombic attractions between partially charged main-chain atoms stabilise the right-handed twist found in most beta-strands, JMB 248 (1995) 374-384. Weak bifurcated H-Bond Ca-Ha...O: Z. S. Derewenda, L. Lee, U. Derewenda, The occurrence of C-H...O hydrogen bonds in proteins, JMB 252 (1995) 248-262. Beta-Sheet Annotation Problem: annotate the beta-sheet regions in proteins from atomic coordinates. Why important? - Beta-sheet prediction algorithm (Chou-Fasman). - Protein classification - Protein function Beta-Sheet Annotation Some algorithms: - DSSP (Kabsch, W. & Sander, C. (1983). Dictionary of protein secondary structure: pattern recognition of hydrogen bonded and geometrical features. Biopolymers, 22, 2577-2637) - DSSPcont (Carter P, Andersen CA, Rost B. (2003). DSSPcont: Continuous secondary structure assignments for proteins. NAR, 31, 3293-3295) - STRIDE (Frishman, D. & Argos, P. (1995). Knowledge-based protein secondary structure assignment. Proteins, 23, 566-579) - DEFINE (Richards, F.M. & Kundrot, C. E. (1988). Identification of structural motifs from protein coordinate data: secondary structure and first-level super secondary structure. Proteins, 3, 71-84) - P-curve (Sklenar, H., Etchebest, C. & Lavery, R. (1989). Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis. Proteins, 6, 46-60) - beta-Spider (Parisien, Major [unpublished]).