Journal
STRUCTURE
Volume 23, Issue 2, Pages 257-269Publisher
CELL PRESS
DOI: 10.1016/j.str.2014.11.021
Keywords
-
Funding
- NIH [R01 CA098799, R01 GM057289, S10 RR022341]
- Burroughs Wellcome Fund Career Award at the Scientific Interface
- University of Missouri
Ask authors/readers for more resources
Skeletal development and invasion by tumor cells depends on proteolysis of collagen by the pericellular metalloproteinase MT1-MMP. Its hemopexin-like (HPX) domain binds to collagen substrates to facilitate their digestion. Spin labeling and paramagnetic nuclear magnetic resonance (NMR) detection have revealed how the HPX domain docks to collagen I-derived triple helix. Mutations impairing triple-helical peptidase activity corroborate the interface. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Part of the interface emerges as unique and potentially targetable for selective inhibition. The triple helix crosses the junction of blades I and II at a 45 degrees angle to the symmetry axis of the HPX domain, placing the scissile Gly similar to Ile bond near the HPX domain and shifted similar to 25 angstrom from MMP-1 complexes. This raises the question of the MT1-MMP catalytic domain folding over the triple helix during catalysis, a possibility accommodated by the flexibility between domains suggested by atomic force microscopy images.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available