The MRH domain suggests a shared ancestry for the mannose 6-phosphate receptors and other N-glycan-recognising proteins

Correspondence The MRH domain suggests a shared ancestry for the mannose 6-phosphate receptors and other N-glycan-recognising proteins Sean Munro N-linked glycans are a prominent feature of many cell surface glycoproteins, but they are also involved in a number of important intracellular processes, including protein folding and degradation in the endoplasmic reticulum (ER), and sorting of proteins to lysosomes and to the plasma membrane [1–3]. All of these processes require the recognition of specific N-glycan structures, and although some of the proteins involved in these processes have been identified, less is known about the structural basis of these recognition events. A crystal structure has been obtained for the carbohydrate recognition domain of the cation-dependent mannose 6-phosphate receptor (CD-MPR) [4]. This receptor sorts lysosomal hydrolases from the trans Golgi network to the late endosome by binding N-glycans on hydrolases that have been modified by the addition of phosphate residues. This role is also performed by the cation-independent MPR whose lumenal domain comprises fifteen repeats of the domain found in one copy in the CD-MPR [5]. We have recently characterised (in this issue of Current Biology [6]) a yeast protein, Mrl1p, that contains a lumenal domain that is related to the mammalian MPRs, and apparently contributes to sorting of hydrolases to the yeast vacuole. This implies that