The role of beta-sheets in the early stages of protein aggregation, specifically amyloid formation, remains unclear. Interpretations of kinetic data have led to a specific model for the role of beta-sheets in polyglutamine aggregation. According to this model, monomeric polyglutamine, which is intrinsically disordered, goes through a rare conversion into an ordered, metastable, beta-sheeted sta...

One of the challenges of protein structure prediction is to identify long-range interactions between amino acids. To reliably predict such interactions, we enumerate, score and rank all βtopologies (partitions of β-strands into sheets, orderings of strands within sheets and orientations of paired strands) of a given protein. We show that the β-topology corresponding to the native structure is, ...

We investigate the formation of β-sheet structures in proteins without sequence-dependent side-chain interactions. To accomplish this, we introduce a model which explicitly incorporates both solvation effects and the angular dependence (on the protein backbone) of hydrogen bond formation. The thermodynamics of this model is studied by exploring the density of states for the entire system and th...

There is increasing recognition that numerous neurodegenerative conditions have the same underlying pathogenetic mechanism, namely a change in protein conformation, where the beta-sheet content is increased. In Alzheimer's disease, amyloid deposition in the form of neuritic plaques and congophilic angiopathy is driven by the conversion of normal soluble amyloid-beta peptide (sA beta) to A beta ...

Kinetic IR spectroscopy was used to reveal beta-sheet formation and water expulsion in the folding of single-chain monellin (SMN) composed of a five-stranded beta-sheet and an alpha-helix. The time-resolved IR spectra between 100 mus and 10 s were analyzed based on two consecutive intermediates, I(1) and I(2), appearing within 100 mus and with a time constant of approximately 100 ms, respective...

Possible stereochemical determinants of the orientation of TBP on the TATA box are discussed using the crystal coordinates of TBP-TATA complexes, which have been determined by other groups. The C-terminal half of the TBP beta-sheet interacts with the TATA site of the DNA, and the N-terminal half with the A-rich site, so that the two sites with distinct curvatures produce a unique fit. Although ...

Steady-state and transient conformational changes upon the thermal unfolding of ubiquitin were investigated with nonlinear IR spectroscopy of the amide I vibrations. Equilibrium temperature-dependent 2D IR spectroscopy reveals the unfolding of the beta-sheet of ubiquitin through the loss of cross peaks formed between transitions arising from delocalized vibrations of the beta-sheet. Transient u...

In an effort to better understand beta-sheet assembly, we have investigated the evolutionary behavior of neighboring residues on adjacent antiparallel beta-strands. Residue pairs were classified according to solvent exposure as well as by whether their backbone NH and C==O groups are hydrogen bonded. The conservation and covariation of 19,241 pairs in 219 sequence alignments was analyzed. Burie...

We here report systematic study of structural dynamics of a 16-residue self-assembling peptide d-EAK16 made of only D-amino acids. We compare these results with its chiral counterpart L-form, l-EAK16. Circular dichroism was used to follow the structural dynamics under various temperature and pH conditions. At 25 degrees C the d-EAK16 peptide displayed a typical beta-sheet spectrum. Upon increas...

Self-trapping of NH-stretch vibrational excitations in synthetic beta-sheet helices is observed using femtosecond infrared pump-probe spectroscopy. In a dialanine-based beta-sheet helix, the transient-absorption change upon exciting the NH-stretch mode exhibits a negative absorption change at the fundamental frequency and two positive peaks at lower frequencies. These two induced-absorption pea...