2MQS

Transient Collagen Triple Helix Binding to a Key Metalloproteinase in Invasion and Development: Spin Labels to Structure

2MQS の概要

• エントリーDOI: 10.2210/pdb2mqs/pdb
• NMR情報: BMRB: 25048
• 分子名称: Matrix metalloproteinase-14, THP_L_and_M_chain, THP_T_chain (3 entities in total)
• 機能のキーワード: protein/protein, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 32744.80

構造登録者

Zhao, Y.,Marcink, T.,Van Doren, S.R. (登録日: 2014-06-26, 公開日: 2015-02-11, 最終更新日: 2023-06-14)

主引用文献

Zhao, Y.,Marcink, T.C.,Sanganna Gari, R.R.,Marsh, B.P.,King, G.M.,Stawikowska, R.,Fields, G.B.,Van Doren, S.R.
Transient collagen triple helix binding to a key metalloproteinase in invasion and development.
Structure, 23:257-269, 2015

PubMed Abstract: 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° angle to the symmetry axis of the HPX domain, placing the scissile Gly∼Ile bond near the HPX domain and shifted ∼25 Å 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.

PubMed: 25651059
DOI: 10.1016/j.str.2014.11.021

実験手法

SOLUTION NMR