Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Academic Article uri icon

Overview

MeSH

  • Binding Sites
  • Crystallography, X-Ray
  • Gene Expression Regulation
  • Humans
  • Jurkat Cells
  • Multiprotein Complexes
  • NF-kappa B
  • Protein Binding
  • Protein Structure, Secondary

MeSH Major

  • Adaptor Proteins, Signal Transducing
  • CARD Signaling Adaptor Proteins
  • Caspases
  • Guanylate Cyclase
  • Neoplasm Proteins
  • Signal Transduction

abstract

  • The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-κB signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to caspases. Here we show that the reconstituted CBM signalosome is a helical filamentous assembly in which substoichiometric CARMA1 nucleates Bcl10 filaments. Bcl10 filament formation is a highly cooperative process whose threshold is sensitized by oligomerized CARMA1 upon receptor activation. In cells, both cotransfected CARMA1/Bcl10 complex and the endogenous CBM signalosome are filamentous morphologically. Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10. Structure-guided mutagenesis confirmed the observed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-κB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization. Copyright © 2013 Elsevier Inc. All rights reserved.

publication date

  • September 26, 2013

has subject area

  • Adaptor Proteins, Signal Transducing
  • Binding Sites
  • CARD Signaling Adaptor Proteins
  • Caspases
  • Crystallography, X-Ray
  • Gene Expression Regulation
  • Guanylate Cyclase
  • Humans
  • Jurkat Cells
  • Multiprotein Complexes
  • NF-kappa B
  • Neoplasm Proteins
  • Protein Binding
  • Protein Structure, Secondary
  • Signal Transduction

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3929958

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2013.08.032

PubMed ID

  • 24074955

Additional Document Info

start page

  • 766

end page

  • 779

volume

  • 51

number

  • 6