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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase region
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Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase region

机译：黏膜相关淋巴组织淋巴瘤易位1（MALT1）半胱天冬酶区域的晶体结构

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摘要

The mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase, a key component of the Carma1/Bcl10/ MALT1 signalosome, is critical for NF-κB 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 car-boxyl-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.
机译：黏膜相关淋巴样组织淋巴瘤易位1（MALT1）半胱天冬酶是Carma1 / Bcl10 / MALT1信号小体的关键组成部分，在多种情况下对于NF-κB信号至关重要。 MALT1被认为是一种支架和蛋白酶，以促进信号传导。然而，对半胱天冬酶作用的生化和结构基础仍然是未知的。在这里，我们报告了MALT1仲半胱天冬酶区域的1.75-A分辨率晶体结构，其中包含仲半胱天冬酶结构域和随后的Ig样结构域。对半胱天冬酶和Ig结构域显示为单个折叠单元，并通过广泛的范德华接触和氢键相互作用。对半胱天冬酰胺酶结构域采用的折叠与经典的半胱天冬酶几乎相同，并且均二聚形成活性蛋白酶。与半胱天冬酶不同，对半胱天冬酶结构域的活性和成熟形式仍然是单个未切割的多肽，并特异性识别结合的肽抑制剂Val-Arg-Pro-Arg。特别地，抑制剂的羧基末端氨基酸Arg由三个高度保守的酸性残基配位。该结构是用于解释以MALT1为代表的半胱氨酸蛋白酶的功能和机制的重要框架。

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    Jong W. Yu; Philip D. Jeffrey; Jun Yong Ha; Xiaolu Yang; Yigong Shi;

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    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544,GlaxoSmithKline, Collegeville, PA 19426;

    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544;

    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544;

    Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;

    Center for Structural Biology, Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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