Newswise — Collagen is a protein that holds our body together. It needs to be moved from cells to connective tissue for its function. Scientists discovered and named the MOTH domain, responsible for recognizing collagen. This finding was reported in the journal Nature Communications on April 20, 2023.
How collagen reaches its site of action
Collagen is crucial for multicellular organisms, providing structural support. In certain mammals, it can constitute up to 30% of body weight. This large protein is produced within cells in the endoplasmic reticulum and must be transported out of the cell to reach the spaces between cells in connective tissue.
The TANGO1 protein family plays a crucial role in recognizing and transporting collagen. These proteins are extremely large, consisting of over 1,000 amino acids. TANGO1 proteins can be found in different cell organelles and the cytoplasm. When a TANGO1 protein detects maturing collagen, it assists in creating a lipid tunnel that facilitates the transportation of collagen from its production site to its intended location for action.
A distinct structure
To carry out its functions, TANGO1 possesses a distinct domain with a unique three-dimensional structure. Previously, this domain was thought to resemble the SH3 structure and considered a substructure. However, using NMR spectroscopy, Oliver Arnolds and Raphael Stoll demonstrated significant structural differences between TANGO1's collagen-recognition domain and the canonical SH3 domain. These distinctions are substantial enough to classify this domain as a separate structure. Consequently, they named it the MOTH domain, an acronym derived from four proteins (MIA, Otoraplin, TALI/TANGO1 homology) that share this specific structure.
The discovery of the MOTH domain sheds light on evolution, as collagen is essential for both vertebrates and invertebrates like insects. The MOTH domain has been present for hundreds of millions of years, but it has undergone changes as invertebrates and vertebrates diverged. This evolution likely corresponds to the emergence of various collagen types. Insects possess a single collagen, whereas humans have 28 different variations. These findings enhance our comprehension of collagen export processes and have potential implications for future fibrosis-related drug advancements.
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