protein beta-sheets - loria
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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
“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...
Beta-Sheet Aggregation
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 ChargeN 0.41Ca 0.02C +0.59Hn +0.27O 0.57Ha +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 AnnotationSome 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])