THE ROLE OF CALCIUM IN THE ORGANIZATION OF FIBRILLIN MICROFIBRILS

The microfibrillar glycoprotein fibrillin has a multidomain structure which contains forty-three epidermal growth factor-like motifs with ca lcium-binding consensus sequences. We have utilized intact microfibril s isolated from human dermal fibroblast cultures to investigate the pu tative influence of bound calcium on microfibrillar organization and i ntegrity. Incubation with EDTA or EGTA rapidly resulted in gross disru ption of microfibril morphology. The treatment induced disorganization of the interbead domains although the regular beaded arrangement was always apparent. These changes were readily reversible on replacing ca lcium, indicating that the treatment had not compromised microfibrilla r integrity. The data localize calcium binding EGF-like repeats to the interbead domains and indicate that lateral packing of fibrillin mono mers is calcium-dependent. This arrangement suggests how mutations in epidermal growth factor-like domains of fibrillin might cause the disr uption in microfibril organization and interactions which underlies th e clinical symptoms of some Marfan syndrome patients.