Open AccessStructural consequences of transforming growth factor beta‐1 activation from near‐therapeutic X‐ray doses
Author(s) -
Stachowski Timothy,
Grant Thomas D.,
Snell Edward H.
Publication year - 2019
Publication title -
journal of synchrotron radiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 99
ISSN - 1600-5775
DOI - 10.1107/s1600577519005113
Subject(s) - small angle x ray scattering , transforming growth factor , x ray , peptide , radiation damage , transforming growth factor beta , dissociation (chemistry) , radiation , irradiation , chemistry , biophysics , materials science , crystallography , scattering , physics , biology , microbiology and biotechnology , biochemistry , optics , nuclear physics
Dissociation of transforming growth factor beta‐1 (TGFβ‐1) from the inhibitory protein latency‐associated peptide (LAP) can occur from low doses of X‐ray irradiation of the LAP–TGFβ‐1 complex, resulting in the activation of TGFβ‐1, and can have health‐related consequences. Using the tools and knowledge developed in the study of radiation damage in the crystallographic setting, small‐angle X‐ray scattering (SAXS) and complementary techniques suggest an activation process that is initiated but not driven by the initial X‐ray exposure. LAP is revealed to be extended when not bound to TGFβ‐1 and has a different structural conformation compared to the bound state. These studies pave the way for the structural understanding of systems impacted at therapeutic X‐ray doses and show the potential impact of radiation damage studies beyond their original intent.