Fig. 5: Proposed mechanism of action of meprin α helices. | Nature Communications

Fig. 5: Proposed mechanism of action of meprin α helices.

From: Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor

Fig. 5

Monomeric full length meprin α dimerises during expression and is proteolytically shed from the membrane bilayer via furin-protease activity. Shed meprin α homodimers oligomerise via interactions of MAM/MATH domains forming large oligomeric helices. These helices function to locally amplify proteolytic activity as well as regulate the extent of activity by sequestrating the protease to specific cellular and tissue locations. Further, oligomerisation putatively improves in vivo stability and half-life. Disruptive mutations that interfere with helix formation or increase rate of depolymerisation are postulated to drive dysregulated and detrimental meprin α function.

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