Abstract
Small leucine-rich repeat proteoglycan (SLRP) proteins have an important role in the organization of the extracellular matrix, especially in the formation of collagen fibrils. However, the mechanism governing the shape of collagen fibrils is poorly understood. Here, we report that the protein Osteomodulin (OMD) of the SLRP family is a monomeric protein in solution that interacts with type-I collagen. This interaction is dominated by weak electrostatic forces employing negatively charged residues of OMD, in particular Glu284 and Glu303, and controlled by entropic factors. The protein OMD establishes a fast-binding equilibrium with collagen, where OMD may engage not only with individual collagen molecules, but also with the growing fibrils. This weak electrostatic interaction is carefully balanced so it modulates the shape of the fibrils without compromising their viability.
Highlights
Small leucine-rich repeat proteoglycan (SLRP) proteins have an important role in the organization of the extracellular matrix, especially in the formation of collagen fibrils
At the core of this mechanism, we found that weak electrostatic forces between OMD and collagen mediate their interaction, leading to an optimal outcome in terms of the diameter and shape of the collagen fibrils produced (Supplementary Fig. 10)
These weak electrostatic forces promote the right balance between sufficient binding levels and quick dissociation rates, allowing the growth of collagen fibrils with sufficient speed
Summary
Small leucine-rich repeat proteoglycan (SLRP) proteins have an important role in the organization of the extracellular matrix, especially in the formation of collagen fibrils. We report that the protein Osteomodulin (OMD) of the SLRP family is a monomeric protein in solution that interacts with type-I collagen. Researches have unveiled a number of proteins that influence the size of collagen fibrils, such as collagen type V or small leucinerich repeat proteoglycans (SLRPs)[1,3,6]. It is unclear how the regulatory mechanism works at the molecular level. We revealed the binding site to collagen and its driving force, suggesting a mechanism that explains the role of OMD in fibril formation
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