Figure 1
From: Expanding the clinical spectrum of COL2A1 related disorders by a mass like phenotype
(a) Schematic representation of COL2A1 protein domains, regions and peptides as well as molecular processing products. The size of protein domains and regions is indicated by amino acid positions within the schema. The localisation of disease-associated COL2A1 amino acid changes p.(Asp65Asn) in the VWFC repeat as well as p.(Lys1312Asn) and p.(Ser1338Asn) in the fibrillar collagen NC1 domain is shown. VWFC, von Willebrand factor (VWF) type C repeat; fibrillar collagen NC1, fibrillar collagen C-terminal non-collagenous (NC1) domain. (b) Visualisation of surface hydrophobicity of the COL2A1 VWFC domain (amino acids 29–98). COL2A1 Asp65 affected in subject 2 and amino acids Val46, Ile54, Val56, Leu63, and Ile67 are labeled (left model). The right model shows the surface hydrophobicity after molecular replacement of Asp65 by asparagine. Different colours indicate the hydrophobicity properties of amino acids. The most polar and charged residues are in cyan and the most hydrophobic residues are in tan. The surface colouring feature of the UCSF Chimera tool (version 1.2) was used61. VWFC, von Willebrand factor (VWF) type C repeat. (c) Structural impact of the COL2A1 p.Lys1312Asn amino acid change. Ribbon representations of the COL2A1 fibrillar collagen NC1 domain show amino acids 1312 and surrounding residues within a radius of 5 Å as well as calcium (green sphere) binding residues as sticks. Sidechains are coloured by element (hydrogen: white; carbon: beige; oxygen: red; nitrogen: blue; cysteine: yellow). The left model shows the structural environment of Lys1312 with Van-der-Waals (VDW) overlaps ≥ -0.4 Å (contacts, green lines), whereas the right model depicts the structural environment of Asn1312 with VDW overlaps ≥ 0.6 Å (clashes, magenta lines). (d) Structural impact of the COL2A1 p.Ser1338Asn amino acid change. Ribbon representations show details of the COL2A1 fibrillar collagen NC1 domain for wild-type (p.Ser1338, left) and mutated (p.Asn1338, right) COL2A1. Colour codes and prediction of VDW contacts and clashes are as mentioned above.
