Zooming in on the hydrophobic ridge of H-2Db: implications for the conformational variability of bound peptides11Edited by I. A. Wilson

HLA-B27 Subtypes Differentially Associated with Disease Exhibit Subtle Structural Alterations

“…The two subtypes exhibit different rotamer conformations for this residue, and the B-factors differ significantly as well. This result is similar to the situation with HLA-A2, where a comparative study of several crystal structures identified peptide positions p4 to p6 to have the highest conformational variability (50).…”

“…However, the present results do not allow the exclusion of a pathogenetic mechanism in which some aberrantly folded forms of HLA-B27 molecules (12,52) interact with KIR3DL1 or an Ig-like transcript molecule. Because salt bridges in hydrophobic environments have a higher stabilizing effect on proteins than hydrogen bonds (50), the change of the salt bridge connecting pLys 9 and Asp 116 in B*2705 to a hydrogen bond to His 116 in B*2709 accounts for the higher B-factors of residues forming the B*2709 F-pocket. This suggests a tighter binding of the peptide in B*2705 and altered dynamic properties of the entire molecule.…”

MHC Class I Bound to an Immunodominant Theileria parva Epitope Demonstrates Unconventional Presentation to T Cell Receptors

“…The overall structure of N*01301 resembles that of other mammalian MHC class I molecules ([3], Fig 2A). Comparison with pMHC structures from other species indicates that the orientation of the N*01301 α3 domain relative to the rest of the MHC class I molecule lies within the range reported for mouse pMHCs [11], [27], but is distinct compared to the average position of human α3 domains, with a 5–7° clockwise rotation relative to the molecular long axis. However, the N*01301 α3 domain does not show the large (14–29°) differences in orientation found between the human molecules and chicken BF2*2101 [8].…”

“…In contrast Trp73 is relatively common in mouse MHC class I molecules, occurring in ∼25% of alleles including L d , L q , D q and D b . In mouse it is always accompanied by Tyr at position 156, which together with Trp at 147 produces a hydrophobic ‘ridge’ that forces the bound peptide out of the groove [11]. A comparable ridge, formed by Tyr152, Trp70 and Tyr9 is seen in the rat RT1-A a molecule [9].…”

“…The N and C termini of bound peptides interact with invariant class I residues at either end of the peptide-binding groove. Peptides are most often between 8 and 10 residues in length, and although longer exceptions that adopt a bulged conformation have been reported in human [10], rat [9] and mouse [11] these have generally been considered very unusual. The peptide specificity exhibited by MHC molecules is dependent on the entire sequence of binding peptides, but is dominated by several key interactions made by so-called anchor residues.…”