3uoa

From Proteopedia

Jump to: navigation, search

Crystal structure of the MALT1 paracaspase (P21 form)

Structural highlights

3uoa is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.75Å
Ligands:CF0, MG, PHQ
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MALT1_HUMAN Note=A chromosomal aberration involving MALT1 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with BIRC2. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.

Function

MALT1_HUMAN Enhances BCL10-induced activation of NF-kappa-B. Involved in nuclear export of BCL10. Binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity. Has ubiquitin ligase activity. MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion.[1] [2] [3]

Publication Abstract from PubMed

The mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase, a key component of the Carma1/Bcl10/MALT1 signalosome, is critical for NF-kappaB signaling in multiple contexts. MALT1 is thought to function as a scaffold and protease to promote signaling; however, the biochemical and structural basis of paracaspase action remains largely unknown. Here we report the 1.75-A resolution crystal structure of the MALT1 paracaspase region, which contains the paracaspase domain and an ensuing Ig-like domain. The paracaspase and the Ig domains appear as a single folding unit and interact with each other through extensive van der Waals contacts and hydrogen bonds. The paracaspase domain adopts a fold that is nearly identical to that of classic caspases and homodimerizes similarly to form an active protease. Unlike caspases, the active and mature form of the paracaspase domain remains a single uncleaved polypeptide and specifically recognizes the bound peptide inhibitor Val-Arg-Pro-Arg. In particular, the carboxyl-terminal amino acid Arg of the inhibitor is coordinated by three highly conserved acidic residues. This structure serves as an important framework for deciphering the function and mechanism of paracaspases exemplified by MALT1.

Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase region.,Yu JW, Jeffrey PD, Ha JY, Yang X, Shi Y Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21004-9. Epub 2011 Dec 7. PMID:22158899[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
9 reviews cite this structure
The paracaspase MALT1: biological function and potential for therapeutic inhibition.
Jaworski et al. (2016)
8 more
32 other articles
No citations found

References

  1. ↑ Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G. Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem. 2001 Jun 1;276(22):19012-9. Epub 2001 Mar 21. PMID:11262391 doi:10.1074/jbc.M009984200
  2. ↑ Zhou H, Wertz I, O'Rourke K, Ultsch M, Seshagiri S, Eby M, Xiao W, Dixit VM. Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature. 2004 Jan 8;427(6970):167-71. Epub 2003 Dec 24. PMID:14695475 doi:10.1038/nature02273
  3. ↑ Rebeaud F, Hailfinger S, Posevitz-Fejfar A, Tapernoux M, Moser R, Rueda D, Gaide O, Guzzardi M, Iancu EM, Rufer N, Fasel N, Thome M. The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat Immunol. 2008 Mar;9(3):272-81. doi: 10.1038/ni1568. Epub 2008 Feb 10. PMID:18264101 doi:10.1038/ni1568
  4. ↑ Yu JW, Jeffrey PD, Ha JY, Yang X, Shi Y. Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase region. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21004-9. Epub 2011 Dec 7. PMID:22158899 doi:10.1073/pnas.1111708108

Contents


PDB ID 3uoa

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/3uoa"
Personal tools