Structural Investigation of Fibrillar Collagen Maturation Using Cryo Electron Microscopy

The biosynthesis of fibrillar collagens (I-III, V, XI) is crucial for development, bone remodeling, and wound healing, while its disruption causes inherited disorders like Osteogenesis Imperfecta and acquired conditions such as fibrosis. The C-terminal proteolytic maturation of procollagens, mediated by a 570 kDa complex of BMP 1 protease, procollagen, and PCPE proteins, is essential for collagen fibrillogenesis and represents a key therapeutic target. Building on preliminary results, including a medium-resolution map of a (mini )procollagen I, this project focuses on improving conditions for assembling and analyzing the maturation complex. This includes testing new crosslinking strategies, increasing the proportion of complexed forms, and optimizing cryo EM grid preparation. These efforts aim to resolve the structure, enhancing understanding of collagen biosynthesis and guiding future drug development.