TY - JOUR
T1 - Umbrella-like Helical Structure of α-Synuclein at the Air-Water Interface Observed with Experimental and Theoretical Sum Frequency Generation Spectroscopy
AU - Strunge, Kris
AU - Burgin, Tucker
AU - Golbek, Thaddeus W.
AU - Roeters, Steven J.
AU - Pfaendtner, Jim
AU - Weidner, Tobias
PY - 2023/12/14
Y1 - 2023/12/14
N2 - The misfolding of α-synuclein (αS) into amyloid aggregates is catalyzed by hydrophobic surfaces and associated with severe brain disorders, such as Parkinson’s disease. Despite the important role of interfaces, the three-dimensional structure of αS at the interfaces is still not clear. We report interface-specific sum frequency generation (SFG) experiments of monomeric αS binding to the air-water interface, a model system for the important hydrophobic surfaces. We combine the SFG spectra with calculations of theoretical spectra based on molecular dynamics simulations to show that αS, which is an intrinsically disordered protein in solution, folds into a defined, mostly helical secondary structure at the air-water interface. The binding pose resembles an umbrella shape, where the C-terminus protrudes into the water phase, while the N-terminus and the NAC region span the canopy at the interface. In this binding pose, αS is prone to aggregate, which could explain the catalytic effect of hydrophobic interfaces and air bubbles on αS fibrillation.
AB - The misfolding of α-synuclein (αS) into amyloid aggregates is catalyzed by hydrophobic surfaces and associated with severe brain disorders, such as Parkinson’s disease. Despite the important role of interfaces, the three-dimensional structure of αS at the interfaces is still not clear. We report interface-specific sum frequency generation (SFG) experiments of monomeric αS binding to the air-water interface, a model system for the important hydrophobic surfaces. We combine the SFG spectra with calculations of theoretical spectra based on molecular dynamics simulations to show that αS, which is an intrinsically disordered protein in solution, folds into a defined, mostly helical secondary structure at the air-water interface. The binding pose resembles an umbrella shape, where the C-terminus protrudes into the water phase, while the N-terminus and the NAC region span the canopy at the interface. In this binding pose, αS is prone to aggregate, which could explain the catalytic effect of hydrophobic interfaces and air bubbles on αS fibrillation.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85180008743&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/38047768
U2 - 10.1021/acs.jpclett.3c02543
DO - 10.1021/acs.jpclett.3c02543
M3 - Article
C2 - 38047768
SN - 1948-7185
VL - 14
SP - 11030
EP - 11035
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 49
ER -