English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  ASC pyrin domain self-associates and binds NLRP3 protein using equivalent binding interfaces.

Oroz, J., Barrera-Vilarmau, S., Alfonso, C., Rivas, G., & de Alba, E. (2016). ASC pyrin domain self-associates and binds NLRP3 protein using equivalent binding interfaces. Journal of Biological Chemistry, 291(37), 19487-19501. doi:10.1074/jbc.M116.741082.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-835D-F Version Permalink: http://hdl.handle.net/21.11116/0000-0001-1C70-2
Genre: Journal Article

Files

show Files
hide Files
:
2350982.pdf (Publisher version), 5MB
Name:
2350982.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2350982_Suppl.docx (Supplementary material), 80KB
Name:
2350982_Suppl.docx
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/vnd.openxmlformats-officedocument.wordprocessingml.document / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Locator:
http://www.jbc.org/content/291/37/19487.full (Publisher version)
Description:
-

Creators

show
hide
 Creators:
Oroz, J.1, Author              
Barrera-Vilarmau, S., Author
Alfonso, C., Author
Rivas, G., Author
de Alba, E., Author
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for Biophysical Chemistry, Max Planck Society, ou_578571              

Content

show
hide
Free keywords: -
 Abstract: Death domain superfamily members typically act as adaptors mediating in the assembly of supramolecular complexes with critical apoptosis and inflammation functions. These modular proteins consist of death domains, death effector domains, caspase recruitment domains, and pyrin domains (PYD). Despite the high structural similarity among them, only homotypic interactions participate in complex formation, suggesting that subtle factors differentiate each interaction type. It is thus critical to identify these factors as an essential step toward the understanding of the molecular basis of apoptosis and inflammation. The proteins apoptosis-associated speck-like protein containing a CARD (ASC) and NLRP3 play key roles in the regulation of apoptosis and inflammation through self-association and protein-protein interactions mediated by their PYDs. To better understand the molecular basis of their function, we have characterized ASC and NLRP3 PYD self-association and their intermolecular interaction by solution NMR spectroscopy and analytical ultracentrifugation. We found that ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. These regions are located at opposite sides of the protein allowing multimeric complex formation previously shown in ASC PYD fibril assemblies. We show that NLRP3 PYD coexists in solution as a monomer and highly populated large-order oligomerized species. Despite this, we determined its monomeric three-dimensional solution structure by NMR and characterized its binding to ASC PYD. Using our novel structural data, we propose molecular models of ASCASC and ASCNLRP3 PYD early supramolecular complexes, providing new insights into the molecular mechanisms of inflammasome and apoptosis signaling.

Details

show
hide
Language(s): eng - English
 Dates: 2016-07-182016-09-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1074/jbc.M116.741082
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Biological Chemistry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 291 (37) Sequence Number: - Start / End Page: 19487 - 19501 Identifier: -