2MZI

NMR Solution Structure of the PRO Form of Human Matrilysin (proMMP-7) in Complex with Anionic Membrane

Summary for 2MZI

• Entry DOI: 10.2210/pdb2mzi/pdb
• Related: 2mze 2mzh
• NMR Information: BMRB: 25489
• Descriptor: Matrilysin, CALCIUM ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: zymogen, hydrolase, membrane-bound form, metalloenzyme, anionic
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix : P09237
• Total number of polymer chains: 1
• Total formula weight: 116470.29

Authors

Prior, S.H.,Van Doren, S.R. (deposition date: 2015-02-12, release date: 2016-09-28, Last modification date: 2024-05-15)

Primary citation

Prior, S.H.,Fulcher, Y.G.,Koppisetti, R.K.,Jurkevich, A.,Van Doren, S.R.
Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors.
Structure, 23:2099-2110, 2015

PubMed Abstract: Matrix metalloproteinase-7 (MMP-7) sheds signaling proteins from cell surfaces to activate bacterial killing, wound healing, and tumorigenesis. The mechanism targeting soluble MMP-7 to membranes has been investigated. Nuclear magnetic resonance structures of the zymogen, free and bound to membrane mimics without and with anionic lipid, reveal peripheral binding to bilayers through paramagnetic relaxation enhancements. Addition of cholesterol sulfate partially embeds the protease in the bilayer, restricts its diffusion, and tips the active site away from the bilayer. Its insertion of hydrophobic residues organizes the lipids, pushing the head groups and sterol sulfate outward toward the enzyme's positive charge on the periphery of the enlarged interface. Fluorescence probing demonstrates a similar mode of binding to plasma membranes and internalized vesicles of colon cancer cells. Binding of bilayered micelles induces allosteric activation and conformational change in the auto-inhibitory peptide and the adjacent scissile site, illustrating a potential intermediate in the activation of the zymogen.

PubMed: 26439767
DOI: 10.1016/j.str.2015.08.013

Experimental method

SOLUTION NMR