Abstract
BackgroundMucosa-associated lymphoid tissue 1 (MALT1) plays an important role in the adaptive immune program. During TCR- or BCR-induced NF-κB activation, MALT1 serves to mediate the activation of the IKK (IκB kinase) complex, which subsequently regulates the activation of NF-κB. Aggregation of MALT1 is important for E3 ligase activation and NF-κB signaling.Principal FindingsUnlike 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 Å2 and contains numerous hydrogen and salt bonds. In conjunction with a second interface, these interactions may represent the basis of MALT1 oligomerization.ConclusionsThe 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.Enhanced version This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.
Highlights
Mucosa-associated lymphoid tissue (MALT) lymphoma is a lowgrade tumor composed mainly of B-cells characterized by chronic inflammation [1,2]
A subset of MALT lymphomas are caused by genetic translocation events that result in fusion proteins of the Nterminal region of cIAP2 and the C-terminal region of Mucosa-associated lymphoid tissue 1 (MALT1)
Wild-type cIAP2 contains tandem baculovirus IAP repeat (BIR) domains followed by a ubiquitin-associated (UBA) domain, Caspase recruitment (CARD) domain and Really Interesting New Gene (RING) domain
Summary
Mucosa-associated lymphoid tissue (MALT) lymphoma is a lowgrade tumor composed mainly of B-cells characterized by chronic inflammation [1,2]. Many of these tumors reside within the stomach epithelium [3]. A subset of MALT lymphomas are caused by genetic translocation events that result in fusion proteins of the Nterminal region of cIAP2 and the C-terminal region of MALT1. Wild-type MALT1 contains a CARD-like death, three Ig-like, a paracaspase domain (Figure 1). Resultant adducts chronically activate the inflammatory NF-kB signaling pathway and predispose or cause disease [4]. How the resultant fusion protein activates NF-kB to cause low grade inflammation in disease remains unclear. Aggregation of MALT1 is important for E3 ligase activation and NF-kB signaling
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