AI Article Synopsis
- MT1-MMP is a zinc-dependent protease that plays a crucial role in cell migration and invasion, and its overexpression is linked to various tumors' aggressiveness.
- The study highlights how the LEM-2/15 antibody inhibits MT1-MMP by binding to a specific surface epitope, indicating a unique mechanism of action.
- This inhibition is shown to effectively control MT1-MMP activity in endothelial cells and at the forefront of migrating cancer cells, suggesting potential therapeutic uses for MT1-MMP modulators.
Article Abstract
Membrane type 1 metalloprotease (MT1-MMP) is a membrane-anchored, zinc-dependent protease. MT1-MMP is an important mediator of cell migration and invasion, and overexpression of this enzyme has been correlated with the malignancy of various tumor types. Therefore, modulators of MT1-MMP activity are proposed to possess therapeutic potential in numerous invasive diseases. Here we report the inhibition mode of MT1-MMP by LEM-2/15 antibody, which targets a surface epitope of MT1-MMP. Specifically, the crystal structures of Fab LEM-2/15 in complex with the MT1-MMP surface antigen suggest that conformational swiveling of the enzyme surface loop is required for effective binding and consequent inhibition of MT1-MMP activity on the cell membrane. This inhibition mechanism appears to be effective in controlling active MT1-MMP in endothelial cells and at the leading edge of migratory cancer cells.
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| http://dx.doi.org/10.1016/j.str.2014.10.012 | DOI Listing |
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