1ITV

Dimeric form of the haemopexin domain of MMP9

1ITV の概要

• エントリーDOI: 10.2210/pdb1itv/pdb
• 分子名称: MMP9, SULFATE ION (3 entities in total)
• 機能のキーワード: mmp9, adaptive molecular recognition, beta propeller, dimer, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix (Probable): P14780
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 45285.30

構造登録者

Cha, H.,Kopetzki, E.,Huber, R.,Lanzendoerfer, M.,Brandstetter, H. (登録日: 2002-02-11, 公開日: 2002-09-04, 最終更新日: 2024-11-20)

主引用文献

Cha, H.,Kopetzki, E.,Huber, R.,Lanzendorfer, M.,Brandstetter, H.
Structural basis of the adaptive molecular recognition by MMP9.
J.Mol.Biol., 320:1065-1079, 2002

PubMed Abstract: Matrix metalloproteinase (MMPs) are critical for the degradation of extracellular matrix components and, therefore, need to be regulated tightly. Almost all MMPs share a homologous C-terminal haemopexin-like domain (PEX). Besides its role in macromolecular substrate processing, the PEX domains appear to play a major role in regulating MMP activation, localisation and inhibition. One intriguing property of MMP9 is its competence to bind different proteins, involved in these regulatory processes, with high affinity at an overlapping recognition site on its PEX domain. With the crystal structure of the PEX9 dimer, we present the first example of how PEX domains accomplish these diverse roles. Blade IV of PEX9 mediates the non-covalent and predominantly hydrophobic dimerisation contact. Large shifts of blade III and, in particular, blade IV, accompany the dimerisation, resulting in a remarkably asymmetric homodimeric structure. The asymmetry provides a novel mechanism of adaptive protein recognition, where different proteins (PEX9, PEX1, and TIMP1) can bind with high affinity to PEX9 at an overlapping site. Finally, the structure illustrates how the dimerisation generates new properties on both a physico-chemical and functional level.

PubMed: 12126625
DOI: 10.1016/S0022-2836(02)00558-2

実験手法

X-RAY DIFFRACTION (1.95 Å)