English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes.

Liepe, J., Holzhütter, H. G., Bellavista, E., Kloetzel, P. M., Stumpf, M. P. H., & Mishto, M. (2015). Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes. eLife, 4: e07545. doi:10.7554/eLife.07545.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-D033-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-D036-5
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Liepe, J.1, Author              
Holzhütter, H. G., Author
Bellavista, E., Author
Kloetzel, P. M., Author
Stumpf, M. P. H., Author
Mishto, M., Author
Affiliations:
1Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_2466694              

Content

show
hide
Free keywords: Bayesian analysis; biophysics; computational biology; experimental design; functional analysis; human; mouse; proteasome regulation; proteasome structure; structural biology; systems biology
 Abstract: Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predicted by the model, and experimentally supported. The analysis suggests that the rate-limiting step of hydrolysis is the transport of the substrates into the proteasome. The transport efficiency varies between human standard- and immuno-proteasomes thereby impinging upon total degradation rate and substrate cleavage-site usage.

Details

show
hide
Language(s): eng - English
 Dates: 2015-09-22
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.7554/eLife.07545
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: eLife
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 4 Sequence Number: e07545 Start / End Page: - Identifier: -