title: Self-oligomerization of the CARD domain prevents complex formation in the CARMA1 signalosome.
abstract: The CARMA1 signalosome composed of CARMA1, BCL10 and MALT1 plays a pivotal role in antigen receptor-mediated lymphocyte activation via the NF-κB pathway. For assembly of the CARMA1 signalosome, BCL10 functions as an adaptor protein that interacts with CARMA1 via the CARD-CARD interaction and with MALT1 via interaction between the C-terminal Ser/Thr-rich region of BCL10 and the first Ig domain of MALT1. Despite the biological importance of the CARMA1 signalosome, structural and biochemical studies have been limited as CARD-containing proteins are prone to aggregation under physiological conditions. In the present study, we successfully purified and characterized CARMA1 CARD and BCL10 CARD and showed that both CARMA1 CARD and BCL10 CARD easily self-oligomerized under physiological conditions. This self-oligomerization of the CARD domain prevents complex formation in the CARMA1 signalosome in vitro. Finally, we propose an interaction mode between CARMA1 CARD and BCL10 CARD based on a structure-based modeling study.
authors.affiliation: School of Biotechnology and the Graduate School of Biochemistry, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Bae
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry* / Q000378:metabolism*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D012995:Solubility; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; D053468:CARD Signaling Adaptor Proteins; C496467:Card11 protein, mouse; D046912:Multiprotein Complexes; D012965:Sodium Chloride