An outcome- defining role for the triple- helical domain in regulating collagen- I assembly

• 成果类型: Article
• 署名作者: Yammine, Kathryn M.; Li, Rasia C.; Borgula, Isabella M.; Abularach, Sophia Mirda; DiChiara, Andrew S.; Raines, Ronald T.; Shoulders, Matthew D.
• 署名单位: Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13199
• DOI: 10.1073/pnas.2412948121
• 发表日期: 2024-11-12
• 关键词: osteogenesis imperfecta; terminal propeptide; disulfide bonds; STABILITY; procollagen; proteostasis; sequence; chains; cells; trimerization

摘要

Collagens are the foundational component of diverse tissues, including skin, bone, cartilage, and basement membranes, and are the most abundant protein class in animals. The fibrillar collagens are large, complex, multidomain proteins, all containing the characteristic triple helix motif. The most prevalent collagens are heterotrimeric, meaning that cells express at least two distinctive procollagen polypeptides that must assemble into specific heterotrimer compositions. The molecular mechanisms ensuring correct heterotrimeric assemblies are poorly understood - even for the most common collagen, type- I. The longstanding paradigm is that assembly is controlled entirely by procollagen assembly has left many questions unanswered. Here, we show that the of procollagen's triple- helical domain plays an essential role in defining procollagen trimer assemblies avoid commitment to triple- helix formation thanks to destabilizing provide a distinctive perspective on the mechanism of procollagen assembly, revealing the molecular basis by which incorrect homotrimer assemblies are avoided and setting the stage for a deeper understanding of the biogenesis of this ubiquitous protein.