Decorin Core Protein (Decoron) Shape Complements Collagen Fibril Surface Structure and Mediates Its Binding

Abstract

Decorin is the archetypal small leucine rich repeat proteoglycan of the vertebrate extracellular matrix (ECM). With its glycosaminoglycuronan chain, it is responsible for stabilizing inter-fibrillar organization. Type I collagen is the predominant member of the fibrillar collagen family, fulfilling both organizational and structural roles in animal ECMs. In this study, interactions between decoron (the decorin core protein) and binding sites in the d and e1 bands of the type I collagen fibril were investigated through molecular modeling of their respective X-ray diffraction structures. Previously, it was proposed that a model-based, highly curved concave decoron interacts with a single collagen molecule, which would form extensive van der Waals contacts and give rise to strong non-specific binding. However, the large well-ordered aggregate that is the collagen fibril places significant restraints on modes of ligand binding and necessitates multi-collagen molecular contacts. We present here a relatively high-resolution model of the decoron-fibril collagen complex. We find that the respective crystal structures complement each other well, although it is the monomeric form of decoron that shows the most appropriate shape complementarity with the fibril surface and favorable calculated energies of interaction. One molecule of decoron interacts with four to six collagen molecules, and the binding specificity relies on a large number of hydrogen bonds and electrostatic interactions, primarily with the collagen motifs KXGDRGE and AKGDRGE (d and e1 bands). This work helps us to understand collagen-decorin interactions and the molecular architecture of the fibrillar ECM in health and disease.

Effects of Cysteine Proteases on the Structural and Mechanical Properties of Collagen Fibers

“…Random areas of control fibers were imaged over different time intervals of incubation in cathepsin activity buffer at pH 5.5 for up to 20 h, which revealed no changes in the fiber structures and minor increases in diameters. Our results are similar to those of previously reported structural SEMbased collagen fibril studies (38,39). SDS-PAGE analysis of supernatants of fiber incubation mixtures did not show any Coomassie-positive fragments, indicating the intactness of the collagen fibers (see also Fig.…”

“…Only recently, the fine structure of collagen fibrils has been better understood (41). The morphology of collagen fibers is characterized by a regular arrangement of fibrils tightly bundled together through GAGmediated proteoglycan interactions as shown in previous reports (15,39,42,43). We and others (24) have previously demonstrated the unique collagenase activity of catK, which is able to cleave at multiple sites within the triple helical region of tropocollagen.…”

Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells

“…A lack of the small leucine-rich proteoglycan decorin has been shown to have a similar effect on collagen fibril formation as the above-described mutations in collagen V (45). Decorin binds to collagen fibrils (48,49), and it was proposed that it tightly controls collagen fibril structure by binding four single collagen molecules (50). Fibromodulin also …”

Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

“…Although the differences in antidecorin antibody-producing cells were not very large, we suppose that the effect is specific because the difference was only present after stimulation with lung-specific ECM and was only present for decorin. Decorin is an important matrix protein in the lung that is known to interact with fibrillar collagens, contributing to collagen fibre network formation [39,40], and can bind transforming growth factor-b, neutralising its profibrotic actions [41,42]. Loss of decorin in the lung may contribute to loosening of the collagen fibre network and higher levels of active transforming growth factor-b.…”