Crystal structure of the second fibronectin type III (FN3) domain from human collagen [alpha]1 type XX

Collagen [alpha]1 type XX, which contains fibronectin type III (FN3) repeats involving six FN3 domains (referred to as the FN#1-FN#6 domains), is an unusual member of the fibril-associated collagens with interrupted triple helices (FACIT) subfamily of collagens. The results of standard protein BLAST suggest that the FN3 repeats might contribute to collagen [alpha]1 type XX acting as a cytokine receptor. To date, solution NMR structures of the FN#3, FN#4 and FN#6 domains have been determined. To obtain further structural evidence to understand the relationship between the structure and function of the FN3 repeats from collagen [alpha]1 type XX, the crystal structure of the FN#2 domain from human collagen [alpha]1 type XX (residues Pro386-Pro466; referred to as FN2-HCXX) was solved at 2.5Å resolution. The crystal structure of FN2-HCXX shows an immunoglobulin-like fold containing a [beta]-sandwich structure, which is formed by a three-stranded [beta]-sheet ([beta]1, [beta]2 and [beta]5) packed onto a four-stranded [beta]-sheet ([beta]3, [beta]4, [beta]6 and [beta]7). Two consensus domains, tencon and fibcon, are structural analogues of FN2-HCXX. Fn8, an FN3 domain from human oncofoetal fibronectin, is the closest structural analogue of FN2-HCXX derived from a naturally occurring sequence. Based solely on the structural similarity of FN2-HCXX to other FN3 domains, the detailed functions of FN2-HCXX and the FN3 repeats in collagen [alpha]1 type XX cannot be identified.