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Title

Hidden α-helical propensity segments within disordered regions of the transcriptional activator CHOP

AuthorsCanales, Ángeles ; Rösinger, Marcel; Sastre, Javier; Felli, Isabella C.; Jiménez-Barbero, Jesús ; Giménez-Gallego, Guillermo ; Fernández-Tornero, Carlos
Issue Date6-Dec-2017
PublisherPublic Library of Science
CitationPLoS ONE 12(12): e0189171 (2017)
AbstractC/EBP-homologous protein (CHOP) is a key determinant of the apoptotic response to endoplasmic reticulum stress or DNA damage. As a member of the C/EBP family, CHOP contains a low complexity N-terminal region involved in transcriptional activation, followed by a bZIP that binds DNA after dimerization. However, in contrast to other C/EBPs, CHOP directs binding to non-canonical C/EBP sites due to unique substitutions in its DNA-binding domain. Herein, we show that the N-terminal region of CHOP is intrinsically unstructured but contains two segments presenting α-helical propensity. One of these segments is conserved in other C/EBPs and mediates essential roles of CHOP, including regulation through phosphorylation. The second segment is placed within a proteolytic-resistant portion of the protein and exhibits reduced flexibility. Moreover, the DNA-binding region of CHOP also contains a segment with α-helical character towards its most N-terminal part. Our results suggest that structure-prone segments scattered within disordered regions may be critical for macromolecular recognition during CHOP-mediated transcriptional activation.
Description15 p.-6 fig.
Publisher version (URL)https://doi.org/10.1371/journal.pone.0189171
URIhttp://hdl.handle.net/10261/161177
DOI10.1371/journal.pone.0189171
E-ISSN1932-6203
Appears in Collections:(CIB) Artículos
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