scholarly journals ATP Binding to PAN or the 26S ATPases Causes Association with the 20S Proteasome, Gate Opening, and Translocation of Unfolded Proteins

2005 ◽  
Vol 20 (5) ◽  
pp. 687-698 ◽  
Author(s):  
David M. Smith ◽  
Galit Kafri ◽  
Yifan Cheng ◽  
David Ng ◽  
Thomas Walz ◽  
...  
Keyword(s):  
Atp Binding ◽  
20S Proteasome ◽  
Unfolded Proteins ◽  
Gate Opening

Peptides that activate the 20S proteasome by gate opening increased oxidized protein removal and reduced protein aggregation

2014 ◽  
Vol 67 ◽  
pp. 304-313 ◽  
Author(s):  
Francisco H. Dal Vechio ◽  
Fernanda Cerqueira ◽  
Ohara Augusto ◽  
Robson Lopes ◽  
Marilene Demasi
Keyword(s):  
Protein Aggregation ◽  
20S Proteasome ◽  
Gate Opening

scholarly journals A Structure-Based Mechanism for DNA Entry into the Cohesin Ring

2020 ◽  
Author(s):  
Torahiko L. Higashi ◽  
Patrik Eickhoff ◽  
Joana S. Simoes ◽  
Julia Locke ◽  
Andrea Nans ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Molecular Basis ◽  
Atp Hydrolysis ◽  
Initial Step ◽  
Sister Chromatid Cohesion ◽  
Chromosome Organization ◽  
Atp Binding ◽  
Structural Framework ◽  
Gate Opening ◽  
Chromatid Cohesion

SUMMARYDespite key roles in sister chromatid cohesion and chromosome organization, the mechanism by which cohesin rings are loaded onto DNA is still unknown. Here, we combine biophysical approaches and cryo-EM to visualize a cohesin loading intermediate in which DNA is locked between two gates that lead into the cohesin ring. Building on this structural framework, we design biochemical experiments to establish the order of events during cohesin loading. In an initial step, DNA traverses an N-terminal kleisin gate that is first opened upon ATP binding and then closed as the cohesin loader locks the DNA against a shut ATPase gate. ATP hydrolysis leads to ATPase gate opening to complete DNA entry. Whether DNA loading is successful, or rather results in loop extrusion, might be dictated by a conserved kleisin N-terminal tail that guides the DNA through the kleisin gate. Our results establish the molecular basis for cohesin loading onto DNA.

scholarly journals Mechanism of Gate Opening in the 20S Proteasome by the Proteasomal ATPases

2008 ◽  
Vol 30 (3) ◽  
pp. 360-368 ◽  
Author(s):  
Julius Rabl ◽  
David M. Smith ◽  
Yadong Yu ◽  
Shih-Chung Chang ◽  
Alfred L. Goldberg ◽  
...  
Keyword(s):  
20S Proteasome ◽  
Gate Opening

PA28γ–20S proteasome is a proteolytic complex committed to degrade unfolded proteins

2021 ◽  
Author(s):  
Jean-Yves Alejandro Frayssinhes ◽  
Fulvia Cerruti ◽  
Justine Laulin ◽  
Angela Cattaneo ◽  
Angela Bachi ◽  
...  
Keyword(s):  
20S Proteasome ◽  
Unfolded Proteins

scholarly journals The YΦ Motif Defines the Structure-Activity Relationships of Human 20S Proteasome Activators

2021 ◽  
Author(s):  
Kwadwo A. Opoku-Nsiah ◽  
Andres H. de la Pena ◽  
Sarah K. Williams ◽  
Nikita Chopra ◽  
Andrej Sali ◽  
...  
Keyword(s):  
Sequence Space ◽  
20S Proteasome ◽  
Recognition Sequence ◽  
Structure Activity Relationships ◽  
Gate Opening ◽  
Structure Activity ◽  
Eukaryotic Proteins ◽  
Proteasome 20S

The 20S proteasome (20S) facilitates turnover of most eukaryotic proteins. Substrate entry into the 20S first requires opening of gating loops through binding of HbYX motifs that are present at the C-termini of certain proteasome activators (PAs). The HbYX motif has been predominantly characterized in the archaeal 20S, whereas little is known about the sequence preferences of the human 20S (h20S). Here, we synthesized and screened ∼120 HbYX-like peptides, revealing unexpected differences from the archaeal system and defining the h20S recognition sequence as the Y-F/Y (YΦ) motif. To gain further insight, we created a functional chimera of the optimized sequence, NLSYYT, fused to the model activator, PA26E102A.A cryo-EM structure of PA26E102A-h20S identified key interactions, including non-canonical contacts and gate-opening mechanisms. Finally, we demonstrated that the YΦ sequence preferences are tuned by valency, allowing multivalent PAs to sample greater sequence space. These results expand the model for termini-mediated gating and provide a template for the design of h20S activators.

Immunolocalization and funtional role of scavenger receptor BI (SR-BI) and ATP-binding cassette A1 (ABC1)

2001 ◽  
Vol 120 (5) ◽  
pp. A678-A678
Author(s):  
I SUC ◽  
M BENDAYAN ◽  
E DELVIN ◽  
L BRISSETTE ◽  
C GAROFALO ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Atp Binding ◽  
Scavenger Receptor Bi ◽  
Atp Binding Cassette

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

2020 ◽  
Author(s):  
Jon Uranga ◽  
Lukas Hasecke ◽  
Jonny Proppe ◽  
Jan Fingerhut ◽  
Ricardo A. Mata
Keyword(s):  
Active Site ◽  
Boronic Acid ◽  
Computational Study ◽  
Ubiquitin Proteasome System ◽  
Bayesian Optimization ◽  
Inhibition Mechanism ◽  
20S Proteasome ◽  
Acid Base ◽  
Ubiquitin Proteasome ◽  
Infection Cycles

The 20S Proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells as well as in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome, an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy and boronic acid containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics and Bayesian optimization of non-bonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach to the reevaluation of non-bonded potentials making use of QM/MM dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the inhibitor.

Sign in / Sign up

Export Citation Format

Share Document