Oligomeric Structure of the MALT1 Tandem Ig-Like Domains

Background: Mucosa-associated lymphoid tissue 1 (MALT1) plays an important role in the adaptive immune program. During TCR- or BCR-induced NF-kappa B activation, MALT1 serves to mediate the activation of the IKK (I kappa B kinase) complex, which subsequently regulates the activation of NF-kappa B. Aggregation of MALT1 is important for E3 ligase activation and NF-kappa B signaling. Principal Findings: Unlike the isolated CARD or paracaspase domains, which behave as monomers, the tandem Ig-like domains of MALT1 exists as a mixture of dimer and tetramer in solution. High-resolution structures reveals a protein-protein interface that is stabilized by a buried surface area of 1256 angstrom(2) and contains numerous hydrogen and salt bonds. In conjunction with a second interface, these interactions may represent the basis of MALT1 oligomerization. Conclusions: The crystal structure of the tandem Ig-like domains reveals the oligomerization potential of MALT1 and a potential intermediate in the activation of the adaptive inflammatory pathway.