Related Experiment Video

Updated: Nov 6, 2025

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
11:27

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

Published on: May 13, 2020

4.1K

MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial

Max T B Clabbers1,2, Susannah Holmes3, Timothy W Muusse4

  • 1Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden.

Nature Communications
|May 11, 2021
PubMed

Insights

Myeloid differentiation primary response 88 (MyD88) and MyD88 adaptor-like (MAL) proteins form critical signaling assemblies. Structural analysis reveals a two-stranded arrangement, crucial for Toll-like receptor (TLR) signaling.

Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Biology

Background:

  • Myeloid differentiation primary response 88 (MyD88) and MyD88 adaptor-like (MAL) are key Toll-like receptor (TLR) adaptors.
  • These adaptors mediate pro-inflammatory cytokine production through signaling pathways.

Purpose of the Study:

  • To determine the structure of MyD88 TIR domain assemblies.
  • To investigate the role of these assemblies in TLR signaling.
  • To compare MicroED and SFX techniques for structure determination.

Main Methods:

  • Microcrystal electron diffraction (MicroED)
  • Serial femtosecond crystallography (SFX)
  • Site-directed mutagenesis

Main Results:

  • The MyD88 TIR domain forms a two-stranded higher-order assembly, similar to MAL TIR.
  • Mutagenesis confirmed the critical role of MyD88 TIR assembly interfaces in TLR4 signaling.
  • MAL was shown to promote unidirectional assembly of MyD88 TIR.

Conclusions:

  • The study provides structural and mechanistic insights into TLR signal transduction.
  • The findings highlight the importance of MyD88 and MAL assembly in immune responses.
  • MicroED and SFX are effective techniques for studying small protein crystals.

More Related Videos

High-resolution Single Particle Analysis from Electron Cryo-microscopy Images Using SPHIRE13:28

High-resolution Single Particle Analysis from Electron Cryo-microscopy Images Using SPHIRE

Published on: May 16, 2017

50.6K
A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

9.3K

Related Concept Videos

X-ray Crystallography02:18

X-ray Crystallography

The size of the unit cell and the arrangement of atoms in a crystal may be determined from measurements of the diffraction of X-rays by the crystal, termed X-ray crystallography.
Diffraction
Diffraction is the change in the direction of travel experienced by an electromagnetic wave when it encounters a physical barrier whose dimensions are comparable to those of the wavelength of the light. X-rays are electromagnetic radiation with wavelengths about as long as the distance between neighboring...
24.8K
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
14.6K