4I1P

Human MALT1 (caspase-IG3) in complex with activity based-probe

Summary for 4I1P

• Entry DOI: 10.2210/pdb4i1p/pdb
• Related: 4I1R
• Descriptor: Mucosa-associated lymphoid tissue lymphoma translocation protein 1, tetrapeptide, ACETATE ION, ... (4 entities in total)
• Functional Keywords: protease, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, perinuclear region : Q9UDY8
• Total number of polymer chains: 4
• Total formula weight: 90469.88

Authors

Schlauderer, F.,Lammens, K.,Hopfner, K.P. (deposition date: 2012-11-21, release date: 2014-07-09, Last modification date: 2023-11-15)

Primary citation

Eitelhuber, A.C.,Vosyka, O.,Nagel, D.,Bognar, M.,Lenze, D.,Lammens, K.,Schlauderer, F.,Hlahla, D.,Hopfner, K.P.,Lenz, G.,Hummel, M.,Verhelst, S.H.,Krappmann, D.
Activity-Based Probes for Detection of Active MALT1 Paracaspase in Immune Cells and Lymphomas.
Chem.Biol., 22:129-138, 2015

PubMed Abstract: MALT1 paracaspase is activated upon antigen receptor stimulation to promote lymphocyte activation. In addition, deregulated MALT1 protease activity drives survival of distinct lymphomas such as the activated B cell type of diffuse large B cell lymphoma (ABC-DLBCL). Here, we designed fluorophore or biotin-coupled activity based-probes (ABP) that covalently modify the active center of MALT1. MALT1-ABPs are exclusively labeling an active modified full length form of MALT1 upon T cell stimulation. Further, despite the CARMA1 requirement for initial MALT1 activation, the MALT1-ABPs show that protease activity is not confined to the high-molecular CARMA1-BCL10-MALT1 (CBM) complex. Using biotin-coupled ABPs, we developed a robust assay for sensitive and selective detection of active MALT1 in cell lines, primary lymphocytes, and DLBCL tumor biopsies. Taken together, MALT1-ABPs represent powerful chemical tools to measure cellular MALT1 activation, determine efficacy of small molecule inhibitors, and classify lymphomas based on MALT1 activity status.

PubMed: 25556945
DOI: 10.1016/j.chembiol.2014.10.021

Experimental method

X-RAY DIFFRACTION (2.403 Å)