A fresh trim provides a new look at the human mannose receptor

The human mannose receptor plays an important role in scavenging a variety of glycans and glycoconjugates, which contributes to both innate and adaptive immunity. However, the fine details of its ligand specificity, and specifically that of carbohydrate-recognition domain 4, the most functionally relevant C-type lectin domain within the receptor, are not completely understood. Feinberg et al. use glycan arrays, crystallography, and a newly trimmed version of carbohydrate-recognition domain 4 to elucidate the molecular mechanisms driving binding specificity. These data contribute to our molecular understanding of Ca(2+)-mediated binding promiscuity in the human mannose receptor and the scavenging role of the receptor itself and highlight unexpected interactions that should inspire further study.