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

Abstract

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.

Authors:
; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
929942
Report Number(s):
BNL-80537-2008-JA
Journal ID: ISSN 0006-2960; TRN: US200822%%1111
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; Journal Volume: 46
Country of Publication:
United States
Language:
English
Subject:
08 HYDROGEN; 36 MATERIALS SCIENCE; CRYSTALLOGRAPHY; CRYSTAL STRUCTURE; DIMERS; DISEASES; HYDROGEN; ILLUMINANCE; IN VITRO; NEUTRONS; NUCLEAR MAGNETIC RESONANCE; PROTEINS; SCATTERING; SHEETS; SURFACTANTS; VISIBLE RADIATION; X-RAY DIFFRACTION; national synchrotron light source

Citation Formats

Hamill,A., Wang, S., and Lee, Jr., C.. Solution Structure of an Amyloid-Forming Protein During Photoinitiated Hexamer-Dodecamer Transitions Revealed Through Small-Angle Neutron Scattering. United States: N. p., 2007. Web. doi:10.1021/bi700233k.
Hamill,A., Wang, S., & Lee, Jr., C.. Solution Structure of an Amyloid-Forming Protein During Photoinitiated Hexamer-Dodecamer Transitions Revealed Through Small-Angle Neutron Scattering. United States. doi:10.1021/bi700233k.
Hamill,A., Wang, S., and Lee, Jr., C.. Mon . "Solution Structure of an Amyloid-Forming Protein During Photoinitiated Hexamer-Dodecamer Transitions Revealed Through Small-Angle Neutron Scattering". United States. doi:10.1021/bi700233k.
@article{osti_929942,
title = {Solution Structure of an Amyloid-Forming Protein During Photoinitiated Hexamer-Dodecamer Transitions Revealed Through Small-Angle Neutron Scattering},
author = {Hamill,A. and Wang, S. and Lee, Jr., C.},
abstractNote = {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.},
doi = {10.1021/bi700233k},
journal = {Biochemistry},
number = ,
volume = 46,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}