PDBsum entry 2mls

Hydrolase

PDB id: 2mls

Contents

Protein chain

164 a.a.

Ligands

PX4 ×125

Metals

_ZN ×2

_CA ×3

References listed in PDB file

Key reference

• Title: Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12.
• Authors: R.K.Koppisetti, Y.G.Fulcher, A.Jurkevich, S.H.Prior, J.Xu, M.Lenoir, M.Overduin, S.R.Van doren.
• Ref.: Nat Commun, 2014, 5, 5552. [DOI no: 10.1038/ncomms6552]
• PubMed id: 25412686

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.