Unfortunately, the presence of a disulfide bond between the molecules clouded the conclusions. The sixth helix of MALT1 CARD domain, in the crystalline state, also sits in its canonical position in another molecule, but not in a swapped dimer interaction. Instead, the helix is involved in a head-to-tail interaction with a neighboring molecule. Consistent with a lack of noticeable homodimeric interactions in the MALT1 crystalline state, a PISA Niltubacin HDAC inhibitor analysis of the MALT1 CARD domain revealed no significant indications of assembly formation in solution. Furthermore, our size-exclusion analysis showed a monomeric behavior. Taken together, this suggested that instead of homodimerization, the CARD domain might be competent to heterodimerize. CARD-containing MALT1 binding partners include Bcl10 and Caspase 8. The interaction with Bcl10 was loosely mapped to the N-terminal region of MALT1. Although the precise mode of interaction was unclear, the CARD domains contributed but were insufficient for interaction. A direct interaction between MALT1 CARD and Bcl10 CARD could not be detected by coimmunoprecipitation, but FRET assay and mutagenesis analysis showed the CARD domain of Bcl10 and MALT1 also contribute to the Bcl10-MALT1 interaction. The surfaces of CARDs are usually polarized with basic surfaces on one side and acidic on the other; an observation that has led some to suggest that this is the basis of putative protein-protein interactions. To evaluate a potential CARD-CARD interaction between MALT1 and Bcl10, we constructed using the 3DJIGSAW server a 3-dimensional model of the human Bcl10 CARD domain using RAIDD as a template. As with MALT1, the Bcl-10 CARD model adopted a polarized charged surface, with helices B, E and F being acidic, and helices A, C, and D being basic. These complementary surface charges may mediate heterodimerization, but further verification undoubtedly would be required. Unfortunately, nothing could be gleaned from phylogenetic analyses, because although the amino acid sequence of the last three helices of the MALT1 CARD domain was conserved, almost all of the conserved residues occurred in the core of the domain; in other words, no large surface-exposed patch of the domain was conserved. Extra-cellular matrix is closely correlated with tumor progression. Hyaluronic acid is a component of the ECM, it is an unsulfated anionic linear glycosaminoglycan polymer comprised of a repeating glucuronic acid and N-acetylglucosamine disaccharide motif. HA keeps tissues hydrated, maintains osmotic balance and cartilage integrity.