Mechanism and specificity of the human paracaspase MALT1

Biochem J. 2012 Apr 1;443(1):287-95. doi: 10.1042/BJ20120035.


The paracaspase domain of MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a component of a gene translocation fused to the N-terminal domains of the cellular inhibitor of apoptosis protein 2. The paracaspase itself, commonly known as MALT1, participates in the NF-κB (nuclear factor κB) pathway, probably by driving survival signals downstream of the B-cell antigen receptor through MALT1 proteolytic activity. We have developed methods for the expression and purification of recombinant full-length MALT1 and its constituent catalytic domain alone. Both are activated by dimerization without cleavage, with a similar dimerization barrier to the distantly related cousins, the apical caspases. By using positional-scanning peptidyl substrate libraries we demonstrate that the activity and specificity of full-length MALT1 is recapitulated by the catalytic domain alone, showing a stringent requirement for cleaving after arginine, and with striking peptide length constraints for efficient hydrolysis. Rates of cleavage (kcat/Km values) of optimal peptidyl substrates are in the same order (10(3)-10(4) M(-1)·s(-1)) as for a putative target protein CYLD. Thus MALT1 has many similarities to caspase 8, even cleaving the putative target protein CYLD with comparable efficiencies, but with diametrically opposite primary substrate specificity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Caspases / biosynthesis*
  • Caspases / chemistry
  • Caspases / isolation & purification
  • Chromatography, Affinity
  • Citrates / chemistry
  • Enzyme Activation
  • Enzyme Activators / chemistry
  • Escherichia coli
  • HEK293 Cells
  • Humans
  • Kinetics
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / isolation & purification
  • Oligopeptides / chemistry
  • Protein Stability
  • Protein Structure, Tertiary
  • Proteolysis
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / isolation & purification
  • Sodium Citrate
  • Substrate Specificity


  • Citrates
  • Enzyme Activators
  • Neoplasm Proteins
  • Oligopeptides
  • Recombinant Fusion Proteins
  • Sodium Citrate
  • Caspases
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein