3V4L

Mouse MALT1(caspase-IG3 domains) in complex with a irreversible peptidic inhibitor

Summary for 3V4L

• Entry DOI: 10.2210/pdb3v4l/pdb
• Related: 3V4O 3V55
• Related PRD ID: PRD_001076
• Descriptor: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 homolog, MALT1 Inhibitor (2 entities in total)
• Functional Keywords: caspase, ig like, hydrolyse, traf6, cytosol, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm, perinuclear region : Q2TBA3
• Total number of polymer chains: 2
• Total formula weight: 45267.53

Authors

Renatus, M.,Wiesmann, C. (deposition date: 2011-12-15, release date: 2012-03-14, Last modification date: 2024-10-30)

Primary citation

Wiesmann, C.,Leder, L.,Blank, J.,Bernardi, A.,Melkko, S.,Decock, A.,D'Arcy, A.,Villard, F.,Erbel, P.,Hughes, N.,Freuler, F.,Nikolay, R.,Alves, J.,Bornancin, F.,Renatus, M.
Structural Determinants of MALT1 Protease Activity.
J.Mol.Biol., 419:4-21, 2012

PubMed Abstract: The formation of the CBM (CARD11-BCL10-MALT1) complex is pivotal for antigen-receptor-mediated activation of the transcription factor NF-κB. Signaling is dependent on MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), which not only acts as a scaffolding protein but also possesses proteolytic activity mediated by its caspase-like domain. It remained unclear how the CBM activates MALT1. Here, we provide biochemical and structural evidence that MALT1 activation is dependent on its dimerization and show that mutations at the dimer interface abrogate activity in cells. The unliganded protease presents itself in a dimeric yet inactive state and undergoes substantial conformational changes upon substrate binding. These structural changes also affect the conformation of the C-terminal Ig-like domain, a domain that is required for MALT1 activity. Binding to the active site is coupled to a relative movement of caspase and Ig-like domains. MALT1 binding partners thus may have the potential of tuning MALT1 protease activity without binding directly to the caspase domain.

PubMed: 22366302
DOI: 10.1016/j.jmb.2012.02.018

Experimental method

X-RAY DIFFRACTION (3.15 Å)