Solution Structure of an Amyloid-Forming Protein During Photoinitiated Hexamer-Dodecamer Transitions Revealed Through Small-Angle Neutron Scattering

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Biochemistry

DOI:https://doi.org/10.1021/bi700233k· OSTI ID:929942

Hamill, A; Wang, S

Shape-reconstruction analysis applied to small angle neutron scattering (SANS) data is used to determine the in vitro conformations of {alpha}-chymotrypsin oligomers that form as a result of partial unfolding with a photoresponsive surfactant. In the presence of the photoactive surfactant under visible light, the native oligomers (dimers or compact hexamers) rearrange into expanded corkscrew-like hexamers. Converting the surfactant to the photopassive form with UV light illumination causes the hexamers to laterally aggregate and intertwine into dodecamers with elongated, twisted conformations containing cross-sectional dimensions similar to amyloid protofilaments. Secondary-structure measurements with FT-IR indicate that this photoinduced hexamer-to-dodecamer association occurs through intermolecular {beta} sheets stabilized with hydrogen bonds, similar to amyloid formation. Traditional structural characterization techniques such as X-ray crystallography and NMR are not easily amenable to the study of these non-native protein conformations; however, SANS is ideally suited to the study of these associated intermediates, providing direct observation of the mechanism of oligomeric formation in an amyloid-forming protein. Combined with photoinitiated hexamer-to-dodecamer associations in the presence of the photoresponsive surfactant, this study could provide unique insight into the amyloidosis disease pathway, as well as novel disease treatment strategies.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 929942
• Report Number(s): BNL--80537-2008-JA
• Journal Information: Biochemistry, Journal Name: Biochemistry Vol. 46; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

08 HYDROGEN
36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
DIMERS
DISEASES
HYDROGEN
ILLUMINANCE
IN VITRO
NEUTRONS
NUCLEAR MAGNETIC RESONANCE
PROTEINS
SCATTERING
SHEETS
SURFACTANTS
VISIBLE RADIATION
X-RAY DIFFRACTION
national synchrotron light source