Geometry Dynamics of α-Helices in Different Class I Major Histocompatibility Complexes

Figure 1

TCR/pMHC. The three HLA molecules studied in this paper are closely related and differ only at amino acid position 116 and/or 156. The X-ray structure of 44:05 in complex with LC13 TCR and ABCD3 peptide (b) is available from http://www.pdb.org/ (PDB-ID: 3KPS) and was used as a template to model similar systems containing 44:03 and 44:02. 44:05 44:02 44:03. (a) Cartoon representation of TCR/pMHC system. The TCR comprises two chains (lime and pink). Each chain is made up of a constant domain and a variable domain. The constant domain faces the membrane. The CDR loops 1–3 are highly polymorphic regions that interact with the MHC. Beta-sheets are the main secondary structural element of the TCR. MHC (grey) class I comprises alpha-helices and beta-sheets. Alpha-helices G-ALPHA1 and G-ALPHA2 together with the underlying beta-sheets comprise the peptide-binding pocket and present digested peptide fragments on the cell surface. (b) Cartoon representation of MHC class I. HLA molecule (grey), peptide (black), tyrosine at position 116 (red), and aspartic acid at position 156 (green). (c, d, and e) Surface representation of MHC binding grooves of B4402 (c), B4403 (d), and B4405 (e). Nonpolar residues (white), basic residues (blue), acidic residues (red), and polar residues (green). The ABCD3 peptide is embraced in the peptide-binding groove displayed in cartoon representation. Helix G-ALPHA2 is dominated by alternating acidic and basic residues. The Y116D mutation introduces a negatively charged residue (compare panel (c) with (b): a red spot appears at the right-hand side of the peptide). The D156L mutation substitutes a charged residue with an apolar residue. Structures are taken from the first frame of MD simulations.

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