Figure 7.

The interface between the ia and pab domains is different between pMHC-I and pMHC-II. (Aa) The pMHC-I structures, here represented by pHLA-A2, have many conserved residues/features at the β₂-m to α1α2 interface (for a complete list of interface residues see Supplementary Files 2A, B ), especially at the pa9 pleat contact region. Also, a contact patch involving paT10 and pbQ6 (both part of the pa9 pleat) and pbT4 and β₂-m ia33 (mostly iaP33) and iaF62 is relatively well conserved. Many of the indicated residue names are shaded with non-white colors, which are based on estimated conservation patterns and are also used in Figure 3 and Supplementary File 1A : black, inherited from the MHC homodimer ancestor; dark blue, ancestral to the I-α1+β₂-m/IIα lineage; purple, ancestral to the I-α2+I-α3/IIβ lineage; light blue, characteristic for the I-α1+β₂-m lineage; pink, characteristic for the I-α2+I-α3 lineage. The α1α2 domain is indicated in surface format with only yellow for pa9 pleat top ridge residues (the ability to see them in this figure is evidence of the pleat being open) and element coloring for the other α1α2 domain residues with red, blue, and gold for O, N, and S atoms, respectively, dark and light green for the C atoms of the pa9 pleat pa8 and pa10 lower ridge residues, respectively, and white for the other C atoms. The β₂-m domain is shown in cyan transparent cartoon format with sidechains of highlighted residues in element color sticks format. The black and white striped region is the α1α2 domain with α3 domain contact region. Residue pbS35 does not directly contact β₂-m but pa(A/S/T)45 is a conserved part of the constellation. (Ab) The β₂-m iaF56 + iaW60 residues (shown in individual, element color spheres format) insert into the pa9 pleat, which can easily be seen from this angle with the α1α2 domain [coloring as in (A)] shown in ribbon format and the sidechains of the pa9 pleat pa8 and pa10 lower ridges in sticks format. The peptide ligand is shown in cartoon format with the Cα’s of P1 and P9 as pink spheres. (Ba) Similar figure as (Aa), but with pHLA-DR1 as a representative structure for pMHC-II. For interactions between the α1β1 and α2 domains, also see Supplementary Files 2A, B . Coloring of residue names is based on conservation patterns as also done in Figure 3 and Supplementary File 1A , and is similar as done in (Aa) except that MHC-IIα-characteristic residues are colored non-dark blue. (Bb) is as (Ab), but showing pHLA-DR1 as a representative pMHC-II structure. The figures Aa-to-Bb show that only in pMHC-I the ia56+ia60 residues penetrate into the pa9 pleat of the pab domain.