Gadolinium MRI contrast compound binding in human plasma glycoprotein afamin

Afamin, a human blood plasma glycoprotein, a putative multi-functional transporter of hydrophobic molecules and a marker for metabolic syndrome, poses multiple challenges for crystallographic structure determination, both practically and in analysis of the models. Several hundred crystals were analysed, and unusual variability in cell volume and difficulty solving the structure despite a ~34% sequence identity with non-glycosylated human serum albumin indicated that the molecule exhibits variable and context-sensitive packing, despite greatly simplified glycosylation in insect cell expressed recombinant afamin. As a promiscuous transporter, afamin can also bind Gadoteridol, a magnetic resonance imaging contrast compound in two sites, one near the human albumin Sudlow-site and a second hitherto unknown binding site.