Expression, purification, cocrystallization and preliminary crystallographic analysis of sucrose octasulfate/human complement regulator factor H SCRs 6-8

Human plasma protein complement factor H (FH) is an inhibitor of the spontaneously activated alternative complement pathway. An allotypic variant of FH, 402His, has been associated with age‐related macular degeneration, the leading cause of blindness in the elderly. Crystals of FH domains 6–8 (FH678) containing 402His have been grown in the presence of a polyanionic sucrose octasulfate ligand (an analogue of the natural glycosaminoglycan ligands of FH) using both native and selenomethionine‐derivatized protein. Native data sets diffracting to 2.3 Å and SeMet data sets of up to 2.8 Å resolution have been collected. An anomalous difference Patterson map reveals self‐ and cross‐peaks from two incorporated Se atoms. The corresponding selenium substructure has been solved.