A5077618067- TGF-β signaling in diseases
- Cell Adhesion Molecules Research
- Connective tissue disorders research
- Developmental Biology and Gene Regulation
- Protease and Inhibitor Mechanisms
- Bone and Dental Protein Studies
- Apelin-related biomedical research
- Kruppel-like factors research
- Signaling Pathways in Disease
- Intestinal and Peritoneal Adhesions
- Collagen: Extraction and Characterization
- Microbial metabolism and enzyme function
- Cellular Mechanics and Interactions
- Cancer-related gene regulation
- Macrophage Migration Inhibitory Factor
University of Manchester
2011-2019
Wellcome Centre for Cell-Matrix Research
2011-2019
Henry Royce Institute
2019
Lysyl oxidases (LOXs) play a central role in extracellular matrix remodeling during development and tumor growth fibrosis through cross-linking of collagens elastin. We have limited knowledge the structure substrate specificity these secreted enzymes. LOXs share conserved C-terminal catalytic domain but differ their N-terminal region, which is composed 4 repeats scavenger receptor cysteine-rich (SRCR) domains LOX-like (LOXL) 2. investigated by X-ray scattering electron microscopy...
Significance Bone morphogenetic proteins (BMPs) are essential signaling molecules important in embryo development and maintaining tissue function adulthood. BMPs regulated outside the cell by inhibitors such as chordin. The structure of chordin is unknown extracellular generally not suitable for high-resolution methods. This study uses electron microscopy other techniques to determine shape human It has a compact horseshoe-shaped with terminal BMP-binding regions protruding prongs. spacing...
TGFβ plays key roles in fibrosis and cancer progression, latency is conferred by covalent linkage to latent binding proteins (LTBPs). LTBP1 essential for folding, secretion, matrix localization activation but little known about its structure due inherent size flexibility. Here we show that adopts an extended conformation with stable matrix-binding N-terminus, central array of 11 calcium-binding EGF domains flexible TGFβ-binding C-terminus. Moreover demonstrate forms short filament-like...
Collagen VI is a ubiquitous extracellular matrix protein that assembles into beaded microfibrils form networks linking cells to the matrix. are typically formed from heterotrimer of α1, α2, and α3 chains. The chain distinct as it contains an extended N terminus with up 10 consecutive von Willebrand factor type A-domains (VWA). Here, we use solution small angle x-ray scattering (SAXS) single particle analysis EM determine nanostructure nine these contiguous A-domains. Both techniques reveal...
Twisted gastrulation (Tsg) and chordin are secreted glycoproteins that function together as BMP (bone morphogenetic protein) antagonists to regulate growth factor signalling. Chordin binds BMPs, preventing them from interacting with their receptors Tsg is known strengthen this inhibitory complex. also acts a agonist by promoting cleavage of tolloid-family proteinases. Here we explore the structural mechanism through which exerts dual activity. We have characterized nanoscale structure human...