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Article Abstract
Collagen IV, an essential and evolutionarily conserved component of basement membranes, is one of the most extensively post-translationally modified proteins. Despite substantial research on fibrillar collagen biosynthesis, our understanding of collagen IV biosynthesis, including its post-translational modifications (PTMs), remains limited. Most PTMs occur intracellularly, primarily within the endoplasmic reticulum (ER). In this review, we examine the molecular ensemble that orchestrates collagen IV biosynthesis in the ER, highlighting the complex interplay between prolyl and lysyl hydroxylases, glycosyltransferases, and molecular chaperones. Furthermore, we discuss how defects in collagen IV and its PTMs contribute to various human pathologies, including Gould and Alport syndromes, fibrosis, and cancer. Understanding collagen IV PTMs is crucial for elucidating the molecular basis of these diseases and improving targeted treatments. By reviewing our knowledge of collagen IV biosynthesis, we illustrate how this evolutionarily conserved yet highly specialized molecular biosynthesis ensemble supports the diverse functions of collagen IV in health and disease.
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| http://dx.doi.org/10.1016/j.matbio.2025.07.002 | DOI Listing |
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