Structure and Interdomain Interactions of a Hybrid Domain: A Disulphide-Rich Module of the Fibrillin/LTBP Superfamily of Matrix Proteins

被引：42

作者：

Jensen, Sacha A. ^{[1
]}

Iqbal, Sarah ^{[1
]}

Lowe, Edward D. ^{[1
]}

Redfield, Christina ^{[1
]}

Handford, Penny A. ^{[1
]}

机构：

[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England

来源：

STRUCTURE | 2009年 / 17卷 / 05期

基金：

英国惠康基金;

关键词：

LARGE LATENT COMPLEX; CALCIUM-BINDING; MARFAN-SYNDROME; MICROFIBRILS; ORGANIZATION; EXPRESSION; COMPONENT; PAIR; GLYCOPROTEIN; MUTATIONS;

D O I：

10.1016/j.str.2009.03.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The fibrillins and latent transforming growth factor-beta binding proteins (LTBPs) form a superfamily of structurally-related proteins consisting of calcium-binding epidermal growth factor-like (cbEGF) domains interspersed with 8-cysteine-containing transforming growth factor beta-binding protein-like (TB) and hybrid (hyb) domains. Fibrillins are the major components of the extracellular 10-12 nm diameter microfibrils, which mediate a variety of cell-matrix interactions. Here we present the crystal structure of a fibrillin-1 cbEGF9-hyb2-cbEGF10 fragment, solved to 1.8 angstrom resolution. The hybrid domain fold is similar, but not identical, to the TB domain fold seen in previous fibrillin-1 and LTBP-1 fragments. Pairwise interactions with neighboring cbEGF domains demonstrate extensive interfaces, with the hyb2cbEGF10 interface dependent on Ca2+ binding. These observations provide accurate constraints for models of fibrillin organization within the 10-12 nm microfibrils and provide further molecular insights into how Ca2+ binding influences the intermolecular interactions and biomechanical properties of fibrillin-1.

引用

页码：759 / 768

页数：10