2MLR
Membrane Bilayer complex with Matrix Metalloproteinase-12 at its Alpha-face
Summary for 2MLR
| Entry DOI | 10.2210/pdb2mlr/pdb |
| Related | 2MLS 2POJ |
| Descriptor | Macrophage metalloelastase, ZINC ION, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | membrane-binding of soluble metalloproteinase mmp-12, catalytic domain, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted, extracellular space, extracellular matrix : P39900 |
| Total number of polymer chains | 1 |
| Total formula weight | 103295.93 |
| Authors | Koppisetti, R.K.,Fulcher, Y.G.,Prior, S.H.,Lenoir, M.,Overduin, M.,Van Doren, S.R. (deposition date: 2014-03-04, release date: 2014-12-03, Last modification date: 2024-05-01) |
| Primary citation | Koppisetti, R.K.,Fulcher, Y.G.,Jurkevich, A.,Prior, S.H.,Xu, J.,Lenoir, M.,Overduin, M.,Van Doren, S.R. Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12. Nat Commun, 5:5552-5552, 2014 Cited by PubMed Abstract: Matrix metalloproteinases (MMPs) regulate tissue remodelling, inflammation and disease progression. Some soluble MMPs are inexplicably active near cell surfaces. Here we demonstrate the binding of MMP-12 directly to bilayers and cellular membranes using paramagnetic NMR and fluorescence. Opposing sides of the catalytic domain engage spin-labelled membrane mimics. Loops project from the β-sheet interface to contact the phospholipid bilayer with basic and hydrophobic residues. The distal membrane interface comprises loops on the other side of the catalytic cleft. Both interfaces mediate MMP-12 association with vesicles and cell membranes. MMP-12 binds plasma membranes and is internalized to hydrophobic perinuclear features, the nuclear membrane and inside the nucleus within minutes. While binding of TIMP-2 to MMP-12 hinders membrane interactions beside the active site, TIMP-2-inhibited MMP-12 binds vesicles and cells, suggesting compensatory rotation of its membrane approaches. MMP-12 association with diverse cell membranes may target its activities to modulate innate immune responses and inflammation. PubMed: 25412686DOI: 10.1038/ncomms6552 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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