Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
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.
Pubmed ID: 26393687
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
The HFSP supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms; topics range from molecular and cellular approaches to systems and cognitive neuroscience. A clear emphasis is placed on novel collaborations that bring biologists together with scientists from fields such as physics, mathematics, chemistry, computer science and engineering to focus on problems at the frontier of the life sciences. The Trust provides funding for research regarding complex biological systems. It offers research grants, post doc fellowships, career development fellowships, and short- long- and cross- disciplinary fellowships. HFSP funding programs are strictly project-related and begin at the postdoctoral level. We have no support for PhD students nor for travel grants to scientific meetings. Nor do we provide sponsorship or funds to organizers of scientific meetings. Research Grants Research Grants are awarded for novel collaborations involving extensive collaboration among teams of scientists working in different countries and in different disciplines. Two types of grants are available: Young Investigators Grants and Program Grants. Postdoctoral Fellowships Postdoctoral Fellowships are available for scientists who wish to work in foreign laboratories, with emphasis on individuals early in their careers who wish to obtain training in a different field of research. Fellows who return to their home countries or move to an HFSP member country that is different from the Fellowship host country are eligible to apply for a Career Development Award. Long-Term Fellowships are for scientists with a Ph.D. degree in the life sciences who wish to broaden their experience through postdoctoral training abroad. Cross-Disciplinary Fellowships are intended for postdoctoral fellows with a Ph.D. degree in the physical sciences, chemistry, mathematics, engineering and computer sciences who wish to receive training in biology. Career Development Awards Career Development Awards are for former HFSP Long-Term or Cross-Disciplinary Fellows who return to their home country or move to an HFSP member country that is different from the host country of their HFSP Fellowship. The award provides support for initiating the fellows'' first independent laboratory.
View all literature mentions