Polymorphism of Amyloid Fibrils Induced by Catalytic Seeding: A Vibrational Circular Dichroism Study

Abstract

Amyloidal protein fibrils occur in many biological events, but their formation and structural variability are understood rather poorly. We systematically explore fibril polymorphism for polyglutamic acid (PGA), insulin and hen egg white lysozyme. The fibrils were grown in the presence of “seeds”, that is fibrils of the same or different protein. The seeds in concentrations higher than about 5 % of the total protein amount fully determined the structure of the final fibrils. Fibril structure was monitored by vibrational circular dichroism (VCD) spectroscopy and other techniques. The VCD shapes significantly differ for different fibril samples. Infrared (IR) and VCD spectra of PGA were also simulated using density functional theory (DFT) and a periodic model. The simulation provides excellent basis for data interpretation and reveals that the spectral shapes and signs depend both on fibril length and twist. The understanding of fibril formation and interactions may facilitate medical treatment of protein misfolding diseases in the future.

Mapping of Supramolecular Chirality in Insect Wings by Microscopic Vibrational Circular Dichroism Spectroscopy: Heterogeneity in Protein Distribution

“…At the thinner part of the membrane (for the right hindwing only), the amide I band also consisted of a couplet that transitions from negative to positive toward lower wavenumbers. On the basis of the observed spectral shapes and peak positions, the protein structure at each position was identified, referring to the reported VCD data for proteins or peptides with distinct secondary structures. ,− The results are summarized in Table .…”

Conformer‐Selective Photoelectron Circular Dichroism

“…Electronic circular dichroism (ECD) is for example routinely used for assessing the secondary structure composition of proteins [1–2] . In the IR range, vibrational circular dichroism (VCD) also provides an exquisite probe of conformation and its modification upon molecular interactions [3–6] . Despite their sensitivity to conformation, these methods are not conformer‐selective, because they rest on direct absorption in the condensed phase where multiple conformers coexist and absorb in the same energy range.…”

“…[1][2] In the IR range, vibrational circular dichroism (VCD) also provides an exquisite probe of conformation and its modification upon molecular interactions. [3][4][5][6] Despite their sensitivity to conformation, these methods are not conformer-selective, because they rest on direct absorption in the condensed phase where multiple conformers coexist and absorb in the same energy range. The obtained spectrum therefore contains the contribution of all the structures populated at the sample temperature.…”

(Resonance) Raman optical activity among chiroptical spectroscopies: Quo vadis?

“…Currently, studies on spontaneous aggregation of molecules and chirality of supramolecular systems are attracting more and more attention due to the important role of macromolecules in biological systems, including the transfer and storage of genetic information [11][12][13][14] and protein folding. 11,12,[15][16][17][18] Moreover, research on the induction and amplification of chirality is also attracting great interest. [19][20][21][22][23] To sum up, several chiroptical techniques based on phenomena related to the interaction of circularly polarized light with a chiral matter are known, and they are powerful complementary tools, often used in combinations to obtain complete structural information of the measured species.…”

“…Thus, the applications of chiroptical spectroscopy are diverse and still expand. Currently, studies on spontaneous aggregation of molecules and chirality of supramolecular systems are attracting more and more attention due to the important role of macromolecules in biological systems, including the transfer and storage of genetic information 11–14 and protein folding 11,12,15–18 . Moreover, research on the induction and amplification of chirality is also attracting great interest 19–23 .…”