8txn | pdb_00008txn

Adaptive mechanism of collagen IV scaffold assembly in Drosophila: crystal structure of recombinant NC1 hexamer

spinqualitylabelsall models 8txn, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8txn is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: 1PE, CL, EDO, MG, PEG, PG4, PGE, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9VMV5_DROME CO4A1_DROME Collagen type IV is specific for basement membranes. Publication Abstract from PubMed Collagen IV is an essential structural protein in all metazoans. It provides a scaffold for the assembly of basement membranes, a specialized form of extracellular matrix, which anchors and signals cells and provides microscale tensile strength. Defective scaffolds cause basement membrane destabilization and tissue dysfunction. Scaffolds are composed of alpha-chains that co-assemble into triple-helical protomers of distinct chain compositions, which in turn oligomerize into supramolecular scaffolds. Chloride ions mediate the oligomerization via NC1 trimeric domains, forming an NC1 hexamer at the protomer-protomer interface. The chloride concentration - "chloride pressure" - on the outside of cells is a primordial innovation that drives the assembly and dynamic stabilization of collagen IV scaffolds. However, a Cl-independent mechanism is operative in Ctenophora, Ecdysozoa, and Rotifera, which suggests evolutionary adaptations to environmental or tissue conditions. An understanding of these exceptions, such as the example of Drosophila, could shed light on the fundamentals of how NC1 trimers direct the oligomerization of protomers into scaffolds. Here, we investigated the NC1 assembly of Drosophila. We solved the crystal structure of the NC1 hexamer, determined the chain composition of protomers, and found that Drosophila adapted an evolutionarily unique mechanism of scaffold assembly that requires divalent cations. By studying the Drosophila case we highlighted the mechanistic role of chloride pressure for maintaining functionality of the NC1 domain in humans. Moreover, we discovered that the NC1 trimers encode information for homing protomers to distant tissue locations, providing clues for the development of protein replacement therapy for collagen IV genetic diseases. Collagen IV of basement membranes: IV. Adaptive mechanism of collagen IV scaffold assembly in Drosophila.,Summers JA, Yarbrough M, Liu M, McDonald WH, Hudson BG, Pastor-Pareja JC, Boudko SP J Biol Chem. 2023 Oct 25:105394. doi: 10.1016/j.jbc.2023.105394. PMID:37890775 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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