Protein Beta-Sheets

Predicted in 1951 by Pauling et Al. using standard bond length and valence angles of H­bonds from small inorganic molecules.

L. Pauling, R. B. Corey, The pleated sheet, a new layer configuration of polypeptide chains, PNAS (USA) 37 (1951) 251­256. 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

Beta­Barrel (1TIM) Beta-Barrel

PDB code 1TIM Beta-Sheet Aggregation

“The fact that natural beta­sheet 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 beta­sheet edges are dangerous, because they are already in the right conformation to interact with any other beta strand they encounter.”

­> beta­sheet amyloid fibers...

Richardson J.S., Richardson D.C., (2002) Natural beta­sheet proteins use negative design to avoid edge­to­edge aggregation, PNAS, 99, 2754­2759. Beta-Sheet Aggregation

Beta­sheet amyloid fibers formation is associated with these neuro­degenerative deseases:

­ Alzheimer (AB peptide) ­ Senile Systemic Amyloidosis (transthyretin protein) ­ Spongiform Encephalopathies (“mad cow”) (prion protein) Beta-Sheet Aggregation

Various strategies employed by beta­sheet to avoid aggregation:

Beta­Barrels: ­ no edge strand!

Parallel Beta­Helix: ­ ends are protected by loops.

Beta­Propellers and Single Sheets: ­ beta­bulge. ­ proline residue. ­ charged residue (that would be buried if dimerized). ­ short edge strand. ­ loop coverage.

Beta­Sandwich: ­ 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. Milner­White, Coulombic interactions between partially charged main­chain atoms not hydrogen­bonded to each other influence the conformations of alpha­helices and antiparallel beta­sheet. A new method for analysing the forces between hydrogen bonding groups in proteins includes all the Coulombic interactions, JMB 248 (1995) 361­373.

P. H. Maccallum, R. Poet, E. J. Milner­White, Coulombic attractions between partially charged main­chain atoms stabilise the right­handed twist found in most beta­strands, JMB 248 (1995) 374­384.

Weak bifurcated H­Bond Ca­Ha...O:

Z. S. Derewenda, L. Lee, U. Derewenda, The occurrence of C­H...O hydrogen bonds in proteins, JMB 252 (1995) 248­262. Beta-Sheet Annotation

Problem: annotate the beta­sheet regions in proteins from atomic coordinates.

Why important?

­ Beta­sheet prediction algorithm (Chou­Fasman). ­ 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, 2577­2637) ­ DSSPcont (Carter P, Andersen CA, Rost B. (2003). DSSPcont: Continuous secondary structure assignments for proteins. NAR, 31, 3293­3295) ­ STRIDE (Frishman, D. & Argos, P. (1995). Knowledge­based protein secondary structure assignment. Proteins, 23, 566­579) ­ DEFINE (Richards, F.M. & Kundrot, C. E. (1988). Identification of structural motifs from protein coordinate data: secondary structure and first­level super secondary structure. Proteins, 3, 71­84) ­ P­curve (Sklenar, H., Etchebest, C. & Lavery, R. (1989). Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis. Proteins, 6, 46­60) ­ beta­Spider (Parisien, Major [unpublished])