MD-2

MD-2, myeloid differentiation factor 2, is a protein that associates with Toll-like receptor 4 in recognition of bacterial lipopolysaccharide. Its ligand-binding pocket and its contacts with the receptor help connect molecular recognition to assembly of a signaling complex. It is distinct from lipopolysaccharide-binding protein and CD14, other participants in recognition of the same microbial material.^[ref]

A 2009 crystal structure revealed two copies of the receptor–MD-2–ligand unit in a symmetric assembly. Five of the examined ligand's six lipid chains occupied the MD-2 pocket; the remaining chain contributed to contact with the neighboring receptor. The location of a chemical group, rather than just the number of ligand molecules present, helped explain the assembly interface.^[ref]

For an original counting example, two such ligand-bound units contain two MD-2 molecules, two Toll-like receptor 4 molecules and two ligand molecules. Six molecules in total do not imply six independent signaling units: their organization into a particular complex is part of the mechanism. The arithmetic counts the modeled assembly; it is not a dose–response law.

A useful experimental comparison would measure ligand binding and a downstream response separately while perturbing the interface. Preserved binding with impaired response would distinguish recognition from productive assembly. This is an experiment-design illustration, not a reported result from the structural study. A crystal structure supplies spatial evidence, while a cellular response assay tests a different level of function.