Dataset Information

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

ABSTRACT: C/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 ?-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 ?-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.

SUBMITTER: Canales A

PROVIDER: S-EPMC5718554 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Canales Ángeles Á Rösinger Marcel M Sastre Javier J Felli Isabella C IC Jiménez-Barbero Jesús J Giménez-Gallego Guillermo G Fernández-Tornero Carlos C

PloS one 20171206 12

C/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 i ...[more]

PMID: 29211802

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Project description:To relate in vivo behavior of fascicle segments within a muscle to their in vitro force-length relationships, we examined the strain behavior of paired segments within each of three vertebrate muscles. After determining in vivo muscle activity patterns and length changes of in-series segments within the semimembranosus muscle (SM) in the American Toad (Bufo americanus) during hopping and within the sternohyoid (SH) muscle in the rat (Rattus rattus) during swallowing, and of spatially separated fascicles within the medial gastrocnemius (MG) muscle in the rat during trotting, we measured their corresponding in vitro (toad) or in situ (rat) force-length relationships (FLRs). For all three muscles, in vivo strain heterogeneity lasted for about 36-57% of the behavior cycle, during which one segment or fascicle shortened while the other segment or fascicle simultaneously lengthened. In the toad SM, the proximal segment shortened from the descending limb across the plateau of its FLR from 1.12 to 0.91 of its optimal length (Lo), while the distal segment lengthened (by 0.04 ± 0.04 Lo) before shortening down the ascending limb from 0.94 to 0.83 Lo. In the rat SH muscle, the proximal segment tended to shorten on its ascending limb from 0.90 to 0.85 Lo while the distal segment tended to lengthen across Lo (0.96-1.12 Lo). In the rat MG muscle, in vivo strains of proximal fascicles ranged from 0.72 to 1.02 Lo, while the distal fascicles ranged from 0.88 to 1.11 Lo. Even though the timing of muscle activation patterns were similar between segments, the heterogeneous strain patterns of fascicle segments measured in vivo coincided with different operating ranges across their FLRs simultaneously, implying differences in force-velocity behavior as well. The three vertebrate skeletal muscles represent a diversity of fiber architectures and functions and suggest that patterns of in vivo contractile strain and the operating range over the FLR in one muscle region does not necessarily represent other regions within the same muscle.

Dataset Information

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

Publications

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

Similar Datasets

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