Characteristic two-dimensional IR spectroscopic features of antiparallel and parallel β-sheet polypeptides: Simulation studies

Abstract

The antiparallel and parallel beta sheets are two of the most abundant secondary structures found in proteins. Although various spectroscopic methods have been used to distinguish these two different structures, the linear spectroscopic measurements could not provide incisive information for distinguishing an antiparallel beta sheet from a parallel beta sheet. After carrying out quantum-chemistry calculations and model simulations, we show that the polarization-controlled two-dimensional (2D) IR photon echo spectroscopy can be of critical use in distinguishing these two different beta sheets. Particularly, the ratio between the diagonal peak and the cross peak is found to be strongly dependent on the quasi-2D array of the amide I local-mode transition dipole vectors. The relative intensities of the cross peaks in the 2D difference spectrum of an antiparallel beta sheet are significantly larger than those of the diagonal peaks, whereas the cross-peak amplitudes in the 2D difference spectrum of a parallel beta sheet are much weaker than the main diagonal-peak amplitudes. A detailed discussion on the origin of the diagonal- and cross-peak intensity distributions of both the antiparallel and parallel beta sheets is presented by examining vibrational exciton delocalization, relative angles between two different normal-mode transition dipoles, and natures of the cross peaks in the 2D difference spectrum.

Two-dimensional IR spectroscopy and segmental 13 C labeling reveals the domain structure of human γD-crystallin amyloid fibrils

“…We assign these features to the antiparallel β-sheets of the Greek keys, because they make up the bulk of the overall protein fold and the assignment is consistent with the observed frequency. The amide I intensity extends to 1;675 cm −1 because the eigenstates of β-sheets cover a wide frequency range, and because other secondary structures contribute to the high frequency side of the spectrum (15,18). Intensity below 1;610 cm −1 is largely due to side chain absorbances and the presence of 13 C at its natural abundance of 1.1% (18).…”

“…Intensity below 1;610 cm −1 is largely due to side chain absorbances and the presence of 13 C at its natural abundance of 1.1% (18). More detailed descriptions of the structural origins of the spectra could be obtained by calculating 2D IR spectra from molecular dynamics simulations of the Protein Data Bank structure (11)(12)(13)(14)(15), but because the folds of the Greek keys are so similar, one domain cannot be distinguished from the other.…”

“…Mechanistic information is obtained from rapid-scan methods that track the kinetics of aggregate formation (6). Spectra can be calculated from molecular dynamics simulations allowing structural models to be tested (11)(12)(13)(14)(15). Isotope-edited 2D IR spectroscopy using 13 C ¼ 18 O labeled backbone amides has been used to study the fibril structure and mechanism of fibril formation for amyloid beta (Aβ) (8) and the human islet amyloid polypeptide (hIAPP) (6,7), as well as many membrane-bound (13,16) and soluble polypeptides (9,10).…”

Two-dimensional IR spectroscopy and isotope labeling defines the pathway of amyloid formation with residue-specific resolution

“…We estimate that not more than 5% of the peptide ensemble can reside in ␤-sheets with Ͼ4 strands, based on the background intensity at 1,617 cm Ϫ1 , where large ␤-sheets absorb. ␤-Sheet aggregates of 3 strands or less could be present during the lag phase, because small ␤-sheets absorb near the random coil at 1,645 cm Ϫ1 (21).…”

Quantification of transition dipole strengths using 1D and 2D spectroscopy for the identification of molecular structures via exciton delocalization: Application to α-helices

“…[3][4][5][6][7][8] In principle, one can fit the amide I absorption band, but it is difficult to be confident in fits because structural disorder causes symmetry forbidden transitions to appear and because the absorption bands themselves have complex lineshapes, among other problematic issues. [9][10][11][12][13][14][15][16] In this paper, we report a method for measuring transition dipole strengths from 1D and 2D IR spectroscopy and illustrate the utility of using transition dipole strengths to identify secondary structure. Transition dipole strengths a) Author to whom correspondence should be addressed.…”