Journal:Acta Cryst D:S2059798324008210
From Proteopedia
Microcrystal electron diffraction structure of Toll-like-receptor 2 TIR domain-nucleated MyD88 TIR domain higher-order assemblyLi, Pacoste, Gu, Thygesen, Stacey, Ve, Kobe, Xu, & Nanson [1] Molecular Tour By refining our data collection methods, we successfully determined the MicroED structure of 8s78 microcrystals, achieving superior resolution (2.85 Å) and completeness (89%) compared to 7beq microcrystals, comparing them. Structural alignment of TLR2TIR- and MALTIR-induced MyD88TIR (four molecules are shown). Notably, both types of assemblies showed distinct conformational differences in regions critical for signaling, such as the BB loop and CD loop, when compared to their monomeric structures. These findings suggest that TLR2TIR and MALTIR interact with MyD88 in a similar manner, promoting the unidirectional nucleation of MyD88TIR assemblies during signaling. This highlights the unique role of TLR2TIR in modulating MyD88 assembly and signaling, offering new insights into the specificity and dynamics of TLR-mediated immune responses. This can be seen in the significant conformational differences (e.g., BB loop, CD loop, αB helix) are observed in several regions when compared with the X-ray and NMR structures of monomeric proteins, e.g., Superposition of the monomer of TLR2TIR induced MyD88TIR structure 8s78 (blue) with the MyD88TIR X-ray structure 4e07 yellow) Superpostion of the monomer of TLR2TIR induced MyD88TIR structure 8s78 (blue) on the MyD88TIR NMR structure 2z5v orange)
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