2Y92

Crystal structure of MAL adaptor protein

Summary for 2Y92

• Entry DOI: 10.2210/pdb2y92/pdb
• Descriptor: TOLL/INTERLEUKIN-1 RECEPTOR DOMAIN-CONTAINING ADAPTER PROTEIN,, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (2 entities in total)
• Functional Keywords: immune system, toll-like receptor signaling, innate immunity
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm (By similarity): P58753
• Total number of polymer chains: 1
• Total formula weight: 16067.36

Authors

Valkov, E.,Stamp, A.,Martin, J.L.,Kobe, B. (deposition date: 2011-02-11, release date: 2011-09-14, Last modification date: 2024-10-16)

Primary citation

Valkov, E.,Stamp, A.,Dimaio, F.,Baker, D.,Verstak, B.,Roversi, P.,Kellie, S.,Sweet, M.J.,Mansell, A.,Gay, N.J.,Martin, J.L.,Kobe, B.
Crystal Structure of Toll-Like Receptor Adaptor Mal/Tirap Reveals the Molecular Basis for Signal Transduction and Disease Protection.
Proc.Natl.Acad.Sci.USA, 108:14879-, 2011

PubMed Abstract: 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 β-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.

PubMed: 21873236
DOI: 10.1073/PNAS.1104780108

Experimental method

X-RAY DIFFRACTION (3.01 Å)