6CLZ

MT1-MMP HPX domain with Blade 4 Loop Bound to Nanodiscs

6CLZ の概要

• エントリーDOI: 10.2210/pdb6clz/pdb
• NMR情報: BMRB: 30425
• 分子名称: Matrix metalloproteinase-14, Apolipoprotein A-I, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (5 entities in total)
• 機能のキーワード: mt1-mmp, mmp-14, nanodisc, lipids, peripheral membrane protein, protease domain, lipid binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 221023.02

構造登録者

Marcink, T.C.,Van Doren, S.R. (登録日: 2018-03-02, 公開日: 2018-12-12, 最終更新日: 2024-05-01)

主引用文献

Marcink, T.C.,Simoncic, J.A.,An, B.,Knapinska, A.M.,Fulcher, Y.G.,Akkaladevi, N.,Fields, G.B.,Van Doren, S.R.
MT1-MMP Binds Membranes by Opposite Tips of Its beta Propeller to Position It for Pericellular Proteolysis.
Structure, 27:281-292.e6, 2019

PubMed Abstract: Critical to migration of tumor cells and endothelial cells is the proteolytic attack of membrane type 1 matrix metalloproteinase (MT1-MMP) upon collagen, growth factors, and receptors at cell surfaces. Lipid bilayer interactions of the substrate-binding hemopexin-like (HPX) domain of MT1-MMP were investigated by paramagnetic nuclear magnetic resonance relaxation enhancements (PREs), fluorescence, and mutagenesis. The HPX domain binds bilayers by blades II and IV on opposite sides of its β propeller fold. The EPGYPK sequence protruding from both blades inserts among phospholipid head groups in PRE-restrained molecular dynamics simulations. Bilayer binding to either blade II or IV exposes the CD44 binding site in blade I. Bilayer association with blade IV allows the collagen triple helix to bind without obstruction. Indeed, vesicles enhance proteolysis of collagen triple-helical substrates by the ectodomain of MT1-MMP. Hypothesized side-by-side MT1-MMP homodimerization would allow binding of bilayers, collagen, CD44, and head-to-tail oligomerization.

PubMed: 30471921
DOI: 10.1016/j.str.2018.10.008

実験手法

SOLUTION NMR