Structural Insights into the Assembly of CARMA1 and BCL10

被引：26

作者：

Li, Siwei ^{[1
,2
]}

Yang, Xue ^{[1
,2
]}

Shao, Juan ^{[1
,2
]}

Shen, Yuequan ^{[1
,2
]}

机构：

[1] Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China

[2] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China

来源：

PLOS ONE | 2012年 / 7卷 / 08期

关键词：

NF-KAPPA-B; ONCOGENIC CARD11 MUTATIONS; ANTIGEN RECEPTOR; CHROMOSOMAL TRANSLOCATION; LYMPHOCYTE DEVELOPMENT; SIGNAL-TRANSDUCTION; ACTIVATION; PHOSPHORYLATION; PROTEIN; KINASE;

D O I：

10.1371/journal.pone.0042775

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The CBM complex (CARMA1, BCL10 and MALT1) plays a crucial role in B and T lymphocyte activation. CARMA1 serves as a scaffold for BCL10, MALT1 and other effector proteins and regulates various signaling pathways related to the immune response. The assembly of CARMA1 and BCL10 is mediated through a CARD-CARD interaction. Here, we report the crystal structure of the CARD domain of CARMA1 at a resolution of 1.75 angstrom. The structure consists of six helices, as previously determined for CARD domains. Structural and computational analysis identified the binding interface between CARMA1-CARD and BCL10-CARD, which consists of a basic patch in CARMA1 and an acidic patch in BCL10. Site-directed mutagenesis, co-immunoprecipitation and an NF-kappa B activation assay confirmed that the interface is necessary for association and downstream signaling. Our studies provide molecular insight into the assembly of CARMA1 and BCL10.

引用

页数：9

共 42 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[2] The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway [J].

Blonska, Marzenna ;

Pappu, Bhanu P. ;

Matsumoto, Reiko ;

Li, Hongxiu ;

Su, Bing ;

Wang, Demin ;

Lin, Xin .

IMMUNITY, 2007, 26 (01) :55-66

[3] The two NF-κB activation pathways and their role in innate and adaptive immunity [J].

Bonizzi, G ;

Karin, M .

TRENDS IN IMMUNOLOGY, 2004, 25 (06) :280-288

[4] MALT1/paracaspase is a signaling component downstream of CARMA1 and mediates T cell receptor-induced NF-κB activation [J].

Che, TJ ;

You, Y ;

Wang, DH ;

Tanner, MJ ;

Dixit, VM ;

Lin, X .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (16) :15870-15876

[5] Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment [J].

Chou, JJ ;

Matsuo, H ;

Duan, H ;

Wagner, G .

CELL, 1998, 94 (02) :171-180

[6] Requirement for CARMA1 in antigen receptor-induced NF-κB activation and lymphocyte proliferation [J].

Egawa, T ;

Albrecht, B ;

Favier, B ;

Sunshine, MJ ;

Mirchandani, K ;

O'Brien, W ;

Thome, M ;

Littman, DR .

CURRENT BIOLOGY, 2003, 13 (14) :1252-1258

[7] Coot:: model-building tools for molecular graphics [J].

Emsley, P ;

Cowtan, K .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2126-2132

[8] CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-κB activation [J].

Gaide, O ;

Favier, B ;

Legler, DF ;

Bonnet, D ;

Brissoni, B ;

Valitutti, S ;

Bron, C ;

Tschopp, J ;

Thome, M .

NATURE IMMUNOLOGY, 2002, 3 (09) :836-843

[9] Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-κB activation [J].

Gaide, O ;

Martinon, F ;

Micheau, O ;

Bonnet, D ;

Thome, M ;

Tschopp, J .

FEBS LETTERS, 2001, 496 (2-3) :121-127

[10] The MAGUK family protein CARD11 is essential for lymphocyte activation [J].

Hara, H ;

Wada, T ;

Bakal, C ;

Kozieradzki, I ;

Suzuki, S ;

Suzuki, N ;

Nghiem, M ;

Griffiths, EK ;

Krawczyk, C ;

Bauer, B ;

D'Acquisto, F ;

Ghosh, S ;

Yeh, WC ;

Baier, G ;

Rottapel, R ;

Penninger, JM .

IMMUNITY, 2003, 18 (06) :763-775

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