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Abstract In eukaryotes, the ubiquitin‐proteasome system is responsible for intracellular protein degradation. Proteins tagged with ubiquitin are recognized by ubiquitin receptors on the 19S regulatory particle (RP) of the 26S proteasome, unfolded, routed through the translocation channel of the RP, and are then degraded in the 20S core particle (CP). Aromatic paddles on the pore‐1 loops of the RP's Rpt subunits grip the substrate and pull folded domains into the channel, thereby unfolding them. The sequence that the aromatic paddles grip while unfolding a substrate is therefore expected to influence the extent of unfolding, and low complexity sequences have been shown to interfere with grip. However, the detailed spatial requirements for grip while unfolding proteins, particularly from the N‐terminus, remain unknown. We determined how the location of glycine‐rich tracts relative to a folded domain impairs unfolding. We find that, in contrast to a previous report, inserting glycine‐rich sequences closer to the folded domain reduced unfolding ability more than positioning them further away. Locations that have the biggest effect on unfolding map onto the regions where the aromatic paddles are predicted to interact with the substrate. Effects on unfolding from locations up to 67 amino acids away from the folded domain suggest that there are additional interactions between the substrate and the proteasome beyond the aromatic paddles that facilitate translocation of the substrate. In sum, this study deepens understanding of the mechanical interactions within the substrate channel by mapping the spacing of interactions between the substrate and the proteasome during unfolding.
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Biomechanical Evaluation of Case Hook Designs for Selector Use in Distribution Centers
Case hooks are tools used in distribution centers by selectors to help them reach and pull products located on the back half of a pallet. This study investigated the postural, electromyographic, and usability responses as 4 handle and 3 tip types were used to pull cases forward on a pallet. The data suggest the pistol grip may be most biomechanically advantageous. With the pistol grip, the rake and conventional tips worked well and had good usability scores.
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- PAR ID:
- 10472494
- Publisher / Repository:
- Sage
- Date Published:
- Journal Name:
- Proceedings of the Human Factors and Ergonomics Society Annual Meeting
- ISSN:
- 2169-5067
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1177/21695067231196241
