期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 36, 页码 14879-14884出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1104780108
关键词
innate immunity; protein-protein interactions; X-ray crystallography
资金
- Wellcome Trust
- Australian Research Council
- NHMRC
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Victorian Government
- BBSRC [BB/G002797/1, BB/G009295/1] Funding Source: UKRI
- MRC [G1000133] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/G009295/1, BB/G002797/1] Funding Source: researchfish
- Medical Research Council [G1000133] Funding Source: researchfish
Initiation of the innate immune response requires agonist recognition by pathogen-recognition receptors such as the Toll-like receptors (TLRs). Toll/interleukin-1 receptor (TIR) domain-containing adaptors are critical in orchestrating the signal transduction pathways after TLR and interleukin-1 receptor activation. Myeloid differentiation primary response gene 88 (MyD88) adaptor-like (MAL)/TIR domain-containing adaptor protein (TIRAP) is involved in bridging MyD88 to TLR2 and TLR4 in response to bacterial infection. Genetic studies have associated a number of unique single-nucleotide polymorphisms in MAL with protection against invasive microbial infection, but a molecular understanding has been hampered by a lack of structural information. The present study describes the crystal structure of MAL TIR domain. Significant structural differences exist in the overall fold of MAL compared with other TIR domain structures: A sequence motif comprising a beta-strand in other TIR domains instead corresponds to a long loop, placing the functionally important BB loop proline motif in a unique surface position in MAL. The structure suggests possible dimerization and MyD88-interacting interfaces, and we confirm the key interface residues by coimmunoprecipitation using site-directed mutants. Jointly, our results provide a molecular and structural basis for the role of MAL in TLR signaling and disease protection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据