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Steven Hayward

Steven Hayward

University of East Anglia, UK

Title: Geometrical Principles of Homeric β-Barrels and β-Helices: Applications to Modelling Amyloid Protofilaments

Biography

Biography: Steven Hayward

Abstract

Examples of homomeric β-helices and β-barrels have recently emerged. Here we have generalized the theory for the shear number in β -barrels to encompass β-helices and homomeric structures. We introduce the concept of the “β-strip” which comprises neighboring strands, parallel or antiparallel and forms the repeating unit that builds the helix.  In this context the shear number is interpreted as the sum of register shifts between neighboring β-strips. This more general approach has allowed us to derive relationships between the helical width, helical pitch, angle between strand direction and helical axis, mass per length, register shift, and number of strands. The validity and unifying power of the method is demonstrated with known structures including the T4 phage spike, cylindrin, and the HET-s(218-289) prion. The relationships have allowed us to predict register shift and number of strands in transthyretin and Alzheimer β(40) amyloid protofilaments from reported dimensions measured by X-ray fiber diffraction which we have used to construct models that comprise a single strip of in-register β-strands folded into a “β-strip helix”. The results suggest that both stabilization of an individual β-strip helix as a protofilament subunit and growth of the protofilament by the joining of subunits end-to-end, would involve the association of the same pair of sequence segments at the same register shift.

T4 phage spike

 

References:

  1. S Hayward, DP Leader, F Al‐Shubailly, EJ Milner‐White (2014) Rings and ribbons in protein structures: Characterization using helical parameters and Ramachandran plots for repeating dipeptides. Proteins 82 (2): 230-239.
  2. S.Hayward, E.J.Milner-White (2011) Simulation of the β- to α-sheet transition results in a twisted sheet for antiparallel and an α-nanotube for parallel strands: Implications for amyloid formation. Proteins 79(11): 3193-3207.
  3. D Taylor, G Cawley, S Hayward (2014) Quantitative method for the assignment of hinge and shear mechanism in protein domain movements. Bioinformatics 30(22): 3189-3196.
  4. S. Hayward and A. Kitao (2015) Monte Carlo Sampling with Linear Inverse-Kinematics for Simulation of Protein Flexible Regions. Journal of Chemical Theory and Computation 11 (8): 3895-3905.
  5. Georgios Iakovou, Steven Hayward, Stephen Laycock (2017) A virtual environment for studying the docking interactions of rigid biomolecules with haptics. Journal of Chemical Information and Modeling 57 (5): 1142–1152.