A, ADAMTS7 protein domains and locations of the glutamate to glutamine
(EQ) catalytic mutant and serine to alanine (S3A) substitutions to prevent
proteoglycan (PG) attachment. Abbreviated ADAMTS7 domains: signal peptide (SP),
disintegrin (Dis), thrombospondin repeats (T), cysteine-rich (Cys-rich),
protease and lacunin (PL). B, expression of full-length (FL) mouse and human
ADAMTS7 3xFlag proteins in the whole cell lysate and secreted in the media under
reducing conditions, detected by western blot using the M2-HRP antibody. High
molecular weight proteoglycan (PG) species are marked in orange. A longer
exposure of the conditioned media was required to visualize the secreted human
ADAMTS7 proteins. C, full-length ADAMTS7 two step purification workflow used to
purify WT S3A active enzyme and EQ S3A negative control protein. D,
Thrombospondin1 in vitro cleavage by purified full-length mouse
ADAMTS7 WT protein (* indicates co-purified auto-cleavage band). Western blots
under reducing conditions to resolve proteolytic TSP1 bands generated by active
ADAMTS7 WT purified enzyme. Presence of the E373Q catalytic mutation in the
purified full-length mouse ADAMTS7 EQ protein ablated the catalytic
activity.