Comprehensive analysis of structural and sequencing data reveals almost unconstrained chain pairing in TCRαβ complex
Fig 5
Contacting residues define mutual orientation of chains in TCRαβ complex.
a. A schematic definition of angles between α and β chains. Principal axes (xα, yα, zα) and (xβ, yβ, zβ) of both TCR chains are computed using the inertia tensor of all atoms of a given chain with the exception of constant domain atoms (top panel); representative orientation of principal axes in real TCR:pMHC complex are shown. Euler angles φ1,2,3 are then computed by superimposing chain centers of mass and computing angles between α and β principal axes (bottom panel). Illustrations were adapted from Wikimedia Commons (https://commons.wikimedia.org/wiki/File:63-T-CellReceptor-MHC.tif by David Goodsell and https://commons.wikimedia.org/wiki/File:Eulerangles.svg by Lionel Brits). b. Testing association between amino acid type (see Methods section and panel d. insert for amino acid cluster definition) and inter-chain angles. Point size shows ANOVA F-score for association between amino acid type and each of three Euler angles across TCR alpha and beta chain positions. The testing is performed for a non-redundant set of TCR chain orientations: all PDB structures with the same VαJαVβJβ are collapsed into a single observation with mean φ1, φ2 and φ3 angles to prevent biases from several complexes with the same TCR. Red circles and labels show contact positions where a significant association between amino acid content and inter-chain angle is present, determined as P < 0.05 (adjusted for multiple testing). c. Representative distribution of φ3 angle values for each amino acid type at α57 position. d. Visualization of all PDB structures aligned to a single representative TCR beta chain. TCR alpha chains are colored according to amino acid type at α57 position.
